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The regulation of apoptosis (the programmed cell death) is dependent on the crucial involvement of BCL2 and BAX. The Bax-248G>A and Bcl-2-938 C>A polymorphic variations in the promoter sequences of the Bax and Bcl-2 gene have been recently associated with low Bax expression, progression to advanced stages, treatment resistance, and shortened overall survival rate in some hematological malignancies, including chronic myeloid leukemia (CML) and other myeloproliferative neoplasms. Chronic inflammation has been linked to various stages of carcinogenesis wherein pro-inflammatory cytokines play diverse roles in influencing cancer microenvironment leading to cell invasion and cancer progression. Cytokines such as TNF-α and IL-8 have been implicated in cancer growth in both solid and hematological malignancies with studies showing their elevated levels in patients. Genomic approaches have in recent years provided significant knowledge with the regard to the association of certain SNPs (single nucleotide polymerphisms) either in a gene or its promoter that can influence its expression, with the risk and susceptibility to human diseases including cancer. This study has investigated the consequences of promoter SNPs in apoptosis genes Bax-248G>A (rs4645878)/Bcl-2-938C>A (rs2279115) and pro-inflammatory cytokines TNF-α rs1800629 G>A/IL-8 rs4073 T>A on the risk and susceptibility towards hematological cancers. The study design has 235 individuals both male and female enrolled as subjects that had 113 cases of MPDs (myeloproliferative disorders) and 122 healthy individuals as controls. The genotyping studies were conducted through ARMS PCR (amplification-refractory mutation system PCR). The Bcl-2-938 C>A polymorphism showed up in 22% of patients in the study, while it was observed in only 10% of normal controls. This difference in genotype and allele frequency between the two groups was significant (p = 0.025). Similarly, the Bax-248G>A polymorphism was detected in 6.48% of the patients and 4.54% of the normal controls, with a significant difference in genotype and allele frequency between the groups (p = 0.048). The results suggest that the Bcl-2-938 C>A variant is linked to an elevated risk of MPDs in the codominant, dominant, and recessive inheritance models. Moreover, the study indicated allele A as risk allele which can significantly increase the risk of MPDs unlike the C allele. In case of Bax gene covariants, these were associated with an increased risk of MPDs in the codominant inheritance model and dominant inheritance model. It was found that the allele A significantly enhanced the risk of MPDs unlike the G allele. The frequencies of IL-8 rs4073 T>A in patients was found to be TT (16.39%), AT (36.88%) and AA (46.72%), compared to controls who were more likely to have frequencies of TT (39.34%), AT (37.70%) and AA (22.95%) as such, respectively. There was a notable overrepresentation of the AA genotype and GG homozygotes among patients compared to controls in TNF-α polymorphic variants, with 6.55% of patients having the AA genotype and 84% of patients being GG homozygotes, compared to 1.63% and 69%, respectively in controls. The data from the current study provide partial but important evidence that polymorphisms in apoptotic genes Bcl-2-938C>A and Bax-248G>A and pro-inflammatory cytokines IL-8 rs4073 T>A and TNF-α G>A may help predict the clinical outcomes of patients and determine the significance of such polymorphic variations in the risk of myeloproliferative diseases and their role as prognostic markers in disease management using a case-control study approach.

Rifampicin resistance in Mycobacterium tuberculosis represents a big public health problem and the ponA1 gene could be related to this. Our study analyzed three secondary databases of 914 M. tuberculosis genomes, which were obtained from samples taken from patients of Lima and Callao cities. The following statistical tests were used to determine statistical association: Chi-square test, prevalence ratio (PR), and odds ratio (OR). We found that the presence of at least one SNP in the ponA1 gene was statistically associated with rifampicin resistance (ρ-values ​​of Chi-square test and OR < 0,05) and it was more likely to find an SNP of this gene in susceptible strains than in rifampicin-resistant strains (ρ-value of PR < 0,05). Likewise, two SNPs (P631S and A516T) were statistically associated with rifampicin resistance (ρ-values ​​of Chi-square test and OR < 0,05). A516T was more likely in resistant strains than susceptible stains, the opposite was found in P631S (ρ-value of PR < 0,05). In conclusion, the SNP A516T is statistically associated with rifampicin resistance and could generate phenotypic changes, which could alter rifampicin tolerance. © 2022, The Author(s) under exclusive licence to Archana Sharma Foundation of Calcutta.

Background: Endometriosis is an estrogen-dependent gynecologic disorder defined by the presence of endometrium outside the uterine cavity [1, 2]. Vitamin D is a steroid hormone known for its importance in various biological processes [3]. Vitamin D may play a direct role in the changes that the endometrium undergoes during the menstrual cycle, as endometrial tissue also expresses enzymes involved in metabolism [3, 4]. The study of genetic polymorphisms in the genes of vitamin D metabolism, namely CYP2R1 rs2060793 and CYP2R1 rs12794714, may contribute to a better understanding to the development of endometriosis and become potential biomarkers of the disease [5, 6]. Objectives: To evaluate the applicability of CYP2R1 rs2060793 and CYP2R1 rs12794714 polymorphisms as potential biomarkers of genetic predisposition to the development of endometriosis. Methods: A case-control study was carried out that included the analysis of 482 women recruited between 2011 and 2018 in two public hospitals in Rio de Janeiro, Brazil, as part of the "Cooperation Protocol" between UEZO and CI-IPOP. Genetic polymorphisms were analysed by allelic discrimination with the StepOnePlusTM real-time PCR system using TaqManTM probes. Results: There was an association between women carrying the A allele of CYP2R1 rs12794714 polymorphism and early development of endometriosis in about 10 years (p=0.026). We also found that women carrying the A allele of the CYP2R1 rs12794714 polymorphism along with a BMI, Proceedings of Research and Practice in Allied and Environmental Health, Vol. 1 N.º 1 (2023): I Jornadas do CISA: 'Jovens Com a Ciência'

Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes. Multivariable logistic regression was used to evaluate the influence of 91 SNPs on urine albumin-to-creatinine ratio (UACR)-related traits and kidney damage (any pathology indicating renal injury), stratifying by diabetes. Weighted PRSs for microalbuminuria and UACR from previous studies were used to calculate the area under the receiver operating characteristic curve (AUROC). CUBN-rs1801239 and DDR1-rs116772905 were associated with all the UACR-derived phenotypes, in both the overall and non-diabetic cohorts, but not with kidney damage. Several SNPs demonstrated different effects in individuals with diabetes compared to those without. SNPs did not improve the AUROC over currently used clinical variables. Many SNPs are associated with UACR or renal injury, suggesting a role in kidney dysfunction, dependent on the presence of diabetes in some cases. However, individual SNPs or PRSs did not improve the diagnostic accuracy for albuminuria or renal injury compared to standard clinical variables.

Ammannia arenaria and A. multifloras, morphologically similar at the seedling stage, are the most common broad-leaved weeds in paddy fields. Our study showed that A. arenaria occupied more space than A. multifloras when competing with rice. However, A. multifloras germination has lower temperature adaptability. No difference in sensitivity to common herbicides between two Ammannia species was observed. Chloroplast (cp) genomes could be conducive to clarify their genetic relationship. The complete cp genome sequences of A. arenaria (158,401 bp) and A. multiflora (157,900 bp) were assembled for the first time. In A. arenaria, there were 91 simple sequence repeats, 115 long repeats, and 86 protein-encoding genes, one, sixteen, and thirty more than those in A. multiflora. Inverted repeats regions expansion and contraction and the phylogenetic tree based on cp genomes demonstrated the closely relationship between the two species. However, in A. arenaria, 20 single nucleotide polymorphisms in the CDS region were detected compared to A. multiflora, which can be used to distinguish the two species. Moreover, there was one unique gene, infA, only in A. arenaria. This study provides reliable molecular resources for future research focusing on the infrageneric taxa identification, phylogenetic resolution, population structure, and biodiversity of Ammannia species.

Since the early 19th century, a substantial amount of jujube (Ziziphus spp.) germplasm has been introduced from China and Europe into the United States. However, due to a lack of passport data, cultivar mislabeling is common and the genetic background of the introduced germplasm remains unknown. In the present study, a low-density SNP array was employed to genotype 204 jujube trees sampled from multiple locations in New Mexico, Texas, Missouri, and Kentucky. Multilocus matching of SNP profiles revealed a significant rate of genetic redundancy among these jujube samples. A total of 14 synonymous groups were detected, comprising 48 accessions. Bayesian clustering analysis and neighbor-joining tree partitioned the US jujube germplasm into two major clusters. The first cluster included cultivated genotypes (Ziziphus jujuba Mill.), whereas the other major cluster comprised the wild/sour jujube (Ziziphus spinosa Hu.). The results also revealed a unique jujube population at Fabens/Tornillo, Texas, and a semi-naturalized population at Tucumcari, NM. These findings will provide valuable guidance to jujube growers and researchers on the effective utilization of jujube germplasm in the horticultural industry.

We have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in terms of changes in plasma lipid levels and CIMT. The study comprised 116 CAD patients with hypercholesterolemia. CIMT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured at baseline and after 6 and 12 months of follow-up, respectively. Genotyping of fifteen lipid-associated GWAS loci was performed by the MassArray-4 System. Linear regression analysis adjusted for sex, age, body mass index, and rosuvastatin dose was used to estimate the phenotypic effects of polymorphisms, and p-values were calculated through adaptive permutation tests by the PLINK software, v1.9. Over one-year rosuvastatin therapy, a decrease in CIMT was linked to rs1689800, rs4846914, rs12328675, rs55730499, rs9987289, rs11220463, rs16942887, and rs881844 polymorphisms (Pperm < 0.05). TC change was associated with rs55730499, rs11220463, and rs6065906; LDL-C change was linked to the rs55730499, rs1689800, and rs16942887 polymorphisms; and TG change was linked to polymorphisms rs838880 and rs1883025 (Pperm < 0.05). In conclusion, polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients.

Background This study aimed to examine possible causal associations between various components of metabolic syndrome and glaucoma-related phenotypes. Methods A two-sample Mendelian randomisation study was conducted with the models of inverse-variance weighted (IVW), maximum likelihood, weighted median and MR-Egger regression. We accessed data from publicly available genome-wide association studies for individual parameters of metabolic syndrome as the exposures and the data for glaucoma and its endophenotypes as the outcomes. Results Among 11 exposures and 6 outcomes examined in this Mendelian randomisation study, only fasting blood glucose level showed evidence of a causal influence on intraocular pressure. Results analysed by the IVW model suggested that each one-SD increase in genetically predicted fasting blood glucose level was significantly associated with 0.80 SD elevation in intraocular pressure (beta: 0.80, 95% CI: 0.38-1.22, p: 2.12e-4). The maximum likelihood model (beta: 0.82, 95% CI: 0.39-1.25, p: 1.616e-4) also supported a significant causal effect. The weighted median model (beta: 0.78, 95% CI: 0.17-1.39, p: 0.012) showed a nominally significant effect whereas the MR-Egger model (beta: 0.63, 95% CI: -0.32-1.59, p: 0.212) showed a consistent direction of effect but was not statistically significant. Several sensitivity analyses indicated no evidence of directional horizontal pleiotropy that would bias the result. Conclusions This Mendelian randomisation study provides evidence for a causal role for genetically determined higher fasting blood glucose level in the development of increased intraocular pressure. This finding could be considered in the monitoring and control of intraocular pressure and may be instrumental in prevention strategies for ocular hypertension.

This study investigated the genetic diversity and population structure of a persimmon (Diospyros kaki Thunb., 2n = 6x = 90) collection in South Korea by evaluating 9751 genome-wide single-nucleotide polymorphisms (SNPs) detected using genotyping-by-sequencing in 93 cultivars. The results of neighbor-joining clustering, principal component analysis, and STRUCTURE analysis based on SNPs indicated clear separation between cultivar groups (pollination-constant nonastringent (PCNA, 40 cultivars), pollination-constant astringent (PCA, 19), pollination-variant nonastringent (PVNA, 23), and the pollination-variant astringent type (PVA, 9)) based on the astringency types, while separation between PVA and PVNA-type cultivars was unclear. Population genetic diversity based on SNPs showed that the proportions of polymorphic SNPs within each group ranged from 99.01% (PVNA) to 94.08% (PVA), and the PVNA group exhibited the highest genetic diversity (He = 3.86 and uHe = 0.397). F (fixation index) values were low ranging from −0.024 (PVA) to 0.176 (PCA) with an average of 0.089, indicating a deficiency of heterozygosity. Analysis of molecular variance (AMOVA) and Fst among cultivar groups indicated that variation within individuals was higher than that among the groups. Pairwise Fst values among the groups ranged from 0.01566 (between PVA and PVNA) to 0.09416 (between PCA and PCNA), indicating a low level of cultivar type differentiation. These findings highlight the potential application of biallelic SNPs in population genetics studies of allopolyploids species and provide valuable insights that may have significant implications for breeding and cultivar identification in persimmon.

A genome-wide association study (GWAS) is a standard approach for understanding the relationship between genetic variants and disease, resulting in a better understanding of disease mechanisms. However, despite the vast contribution of GWAS to our knowledge and understanding of human biology, our ability to interpret these findings has not yet been fully developed. This is primarily because most disease-disposed regions are found within the non-coding regions of the genome, which affect regulatory elements such as enhancers and promoters. There is currently no clear path to identify causal regulatory SNPs and to link these to the genes and cell types they affect. This thesis work focuses on first understanding scATAC-seq as a technology and its outputs and then taking advantage of its potential power to prioritise non-coding genetic variants and cell types. I have deeply reviewed and explored single-cell open chromatin epigenetics, which led to discovering the effect of the Tn5 cutting pattern on providing different levels of information from scATAC-seq. I developed a mathematical strategy to remove nucleosomal background from scATAC-seq data, increasing the data resolution and enabling the accurate identification of TF-bound regions. We successfully built an analytical platform, Avocato, which provides a complete solution to understand the relationship between non-coding genetic variants and their affected diseases. Avocato is not only capable of analysing and visualising scATAC-seq data but also removes background noise resulting in high-resolution data to be used in prioritising non-coding genetic variants and cell types. Additionally, Avocato allows users to interact with their analysis and prioritisation results interactively in a user-friendly interface. Together this thesis builds on existing technologies, bringing us one step closer to fully understanding GWAS findings and functional studies and elucidating the mechanisms of common human diseases.

Comparing genetic variation between populations can provide insight into selective pressures in the environment. The Mouse Diversity Genotyping Array (MDGA) is a low-cost, high-throughput tool developed to capture and analyze variation at single nucleotide polymorphic (SNP) loci in inbred mouse strains. However, its ability to assess genetic variation in non-inbred mice and associate SNPs with the environment has not been extensively studied. First, SNPs between laboratory inbred and wild-caught mice were compared. No SNPs were associated with either macroenvironment. Instead, SNPs reflected genealogy and inbreeding strategies, consistent with the MDGA’s intended use. Second, mutations at SNP loci were compared between a mouse model of breast cancer metastasis with and without Receptor for Hyaluronan-Mediated Motility (RHAMM). Genetic homogeneity observed in the lung microenvironment without RHAMM is consistent with strong purifying selection. In conclusion, the MDGA is effective for associating SNPs with the environment only when selective pressures exceed genetic background effects.

Single nucleotide polymorphisms in non-HLA genes are involved in the development of rheumatoid arthritis (RA). SNPS in genes: PADI4 (rs2240340), STAT4 (rs7574865), CD40 (rs4810485), PTPN22 (rs2476601), and TRAF1 (rs3761847) have been described as risk factors for the development of autoimmune diseases, including RA. This study aimed to assess the prevalence of polymorphisms of these genes in the Polish population of patients with rheumatoid arthritis as compared to healthy controls. 324 subjects were included in the study: 153 healthy subjects and 181 patients from the Department of Rheumatology, Medical University of Lodz who fulfilled the criteria of rheumatoid arthritis diagnosis. Genotypes were determined by Taqman SNP Genotyping Assay. rs2476601 (G/A, OR = 2.16, CI = 1.27–3.66; A/A, OR = 10.35, CI = 1.27–84.21), rs2240340 (C/T, OR = 4.35, CI = 2.55–7.42; T/T, OR = 2.80, CI = 1.43–4.10) and rs7574865 (G/T, OR = 1.97, CI = 1.21–3.21; T/T, OR = 3.33, CI = 1.01–11.02) were associated with RA in the Polish population. Rs4810485 was also associated with RA, however after Bonferroni’s correction was statistically insignificant. We also found an association between minor alleles of rs2476601, rs2240340, and rs7574865 and RA (OR = 2.32, CI = 1.47–3.66; OR = 2.335, CI = 1.64–3.31; OR = 1.88, CI = 1.27–2.79, respectively). Multilocus analysis revealed an association between CGGGT and rare (below 0.02 frequency) haplotypes (OR = 12.28, CI = 2.65–56.91; OR = 3.23, CI = 1.63–6.39). In the Polish population, polymorphisms of the PADI4, PTPN22, and STAT4 genes have been detected, which are also known risk factors for RA in various other populations.

The pathophysiology of atopic dermatitis (AD) is complex, multifactorial, and not fully understood. Genes encoding collagens, the most abundant proteins in the extracellular matrix (ECM), may play a potential role in the pathogenesis of AD. Our study aimed to estimate the associations between Col3A1/rs1800255, Col6A5 /29rs12488457, and Col8A1/rs13081855 polymorphisms and the occurrence, course, and features of AD in the Polish population. Blood samples were collected from 157 patients with AD and 111 healthy volunteers. The genotype distribution of the investigated collagens genes did not differ significantly between the AD and control subjects (p > 0.05). The AA genotype of Col3A1/rs1800255 was significantly associated with the occurrence of mild SCORAD (OR = 0.16; 95% Cl: 0.03–0.78; p = 0.02) and mild pruritus (OR = 18.5; 95% Cl: 3.48–98.40; p = 0.0006), while the GG genotype was significantly associated with severe SCORAD (OR = 6.6; 95% Cl: 1.23–32.35; p = 0.03). Regarding Col6A5/29rs12488457 polymorphism, the average SCORAD score was significantly lower in the group of patients with genotype AA than in patients with the AC genotype (39.8 vs. 53.4; p = 0.04). Nevertheless, both average SCORAD scores were high, and represent the moderate and severe grades of the diseases, respectively. The single nucleotide polymorphisms (SNPs) of COL3A1/ rs1800255 and Col6A5/29rs12488457 seem to be associated with AD courses and symptoms, suggesting new disease biomarkers. The modulation of collagens, the major component of the ECM, may serve as a therapeutic target of AD in the future.

Atopy is an exaggerated IgE-mediated immune response to foreign antigens in which metabolic abnormalities of the leukotrienes (LTs) pathway play a crucial role. Recent studies have described sex as a key variable in LT biosynthesis, partly explaining why treatment with anti-LT drugs in atopic subjects leads to better control of symptoms in women. In addition, variability in LT production is often associated with single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase (ALOX5) gene, which encodes the leukotriene-synthesizing enzyme machinery, 5-lipoxygenase (5-LO). This study aimed to investigate whether two SNPs of ALOX5 are implicated in sex differences in allergic diseases in a prospective cohort of 150 age- and sex-matched atopic and healthy subjects. Rs2029253 and rs2115819 were genotyped using allele-specific RT-PCR, and serum levels of 5-LO and LTB4 were measured by ELISA. Both polymorphisms are significantly more common in women than in men, and their influences on LT production vary as a function of sex, leading to a decrease in men’s and an increase in women’s serum levels of 5-LO and LTB4. These data represent a new resource for understanding sex-related differences in lung inflammatory diseases, partly explaining why women are more likely to develop allergic disorders than men.

To date, there has been great progress in understanding the genetic basis of ischemic stroke (IS); however, several aspects of the condition remain underexplored, including the influence of genetic factors on post-stroke outcomes and the identification of causative loci. We proposed that an analysis of the results obtained from animal models of brain ischemia could be helpful. To this end, we developed a bioinformatic approach for exploring single-nucleotide polymorphisms (SNPs) in human orthologs of rat genes expressed differentially after induced brain ischemia. Using this approach, we identified and analyzed 11 SNPs from 6 genes in 553 Russian individuals (331 patients with IS and 222 controls). We assessed the association of SNPs with the risk of IS and IS outcomes. We found that the SNPs rs858239 (GPNMB), rs907611 (LSP1), and rs494356 (TAGLN) were associated with different parameters of IS functional outcomes. In addition, the SNP rs1261025 (PDPN) was associated significantly with IS itself (p = 0.0188, recessive model). All these associations were demonstrated for the first time. Analysis of the literature suggests that they should be characterized as being inflammation related. This supports the pivotal role of inflammation in both the incidence of stroke and post-stroke outcomes. We believe the findings reported here will help with stroke prognosis in the future.

In the last 20 years, there has been interest in modifying this fatty acid profile to increase the content in polyunsaturated fatty acids which are healthier for human health. However, long chain polyunsaturated fatty acids cause milk fat depression. We observed a wide variation in the sensitivity of cows to induced milk fat depression caused by feeding on linseed-rich diets. We identified 15 genes as key gene regulators harboring SNP in cows fed the linseed-rich diet. The selected genes are novel candidates to be involved in the resistance or sensitivity of dairy cows to milk fat depression, and open the opportunity to select cows genetically resistant to milk fat depression. Feeding linseed to dairy cows results in milk fat depression (MFD), but there is a wide range of sensitivity among cows. The objectives of this study were to identify target genes containing SNP that may play a key role in the regulation of milk fat synthesis in cows resistant or sensitive to MFD. Four cows were selected from a dairy farm after a switch from a control diet to a linseed-rich diet; two were resistant to MFD with a high milk fat content in the control (4.06%) and linseed-rich (3.90%) diets; and two were sensitive to MFD with the milk fat content decreasing after the change from the control (3.87%) to linseed-rich (2.52%) diets. Transcriptome and SNP discovery analyses were performed using RNA-sequencing technology. There was a large number of differentially expressed genes in the control (n = 1316) and linseed-rich (n = 1888) diets. Of these, 15 genes were detected as key gene regulators and harboring SNP in the linseed-rich diet. The selected genes MTOR, PDPK1, EREG, NOTCH1, ZNF217 and TGFB3 may form a network with a principal axis PI3K/Akt/MTOR/SREBP1 involved in milk fat synthesis and in the response to diets that induced MFD. These 15 genes are novel candidate genes to be involved in the resistance or sensitivity of dairy cows to milk fat depression.

Bladder cancer (BC) is the 10th most common form of cancer globally, but its complete aetiology is still unknown. Nevertheless, there is evidence that chronic inflammation plays a role in the development and progression of BC. Therefore, the presented study aimed to detect a potential association between selected single nucleotide polymorphisms (SNPs)—rs1800797 and rs2069845 in IL-6 and rs2227307 in IL-8—and BC development, as well as to identify the impact of BC on the level of expression and methylation of IL-6 and IL-8 promoters in PBMCs with the use of the TaqMan SNP genotyping assay, TaqMan gene expression assay, and methylation-sensitive high-resolution melting techniques. We did not find any association between the genotypes and combined genotypes of all studied polymorphisms and the occurrence of BC. However, we found that BC patients were characterised by decreased IL-6 and IL-8 mRNA expression levels compared to the controls. Additionally, the methylation status of the IL-6 promoter was higher in controls than in BC patients. Our findings suggest that inflammation may be involved in the development and progression of BC.

A better assessment of prostate cancer (PrCa) risk is needed to improve screening. The PROFILE pilot study explored the feasibility of single nucleotide polymorphism profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH., Background. A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. Patients and Methods. A total of 100 men aged 40–69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. Results. Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). Conclusion. The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress. Implications for Practice: Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.

Diabetic Retinopathy (DR) is a leading cause of preventable visual impairment in the working age population. Despite the increasing prevalence of DR, there remain gaps in our understanding of its pathophysiology. This is a prospective case-control study comparing the genetic profiles of patients with no DR vs. non-proliferative DR (NPDR) focusing on intraretinal microvascular abnormalities (IRMA) and venous beading (VB) in Caucasians. A total of 596 participants were recruited to the study; 199 with moderate/severe NPDR and 397 with diabetes for at least 5 years without DR. Sixty-four patients were excluded due to technical issues. In total, 532 were analysed; 181 and 351 were in the NPDR group and no DR group, respectively. Those with severe IRMA and VB had distinctly different genetic profiles from each other and from the no DR group, which further supports the theory that these two features of DR might have different etiologies. This also suggests that IRMA and VB are independent risk factors for the development of PDR and may have different pathophysiologies. If these findings are confirmed in larger studies, this could pave the way for personalised treatment options for those more at risk of developing different features of NPDR.

Context The joint associations of maternal and fetal single nucleotide polymorphisms (SNPs) of lipid metabolic genes with the risk of maternal supraphysiological hypercholesterolemia (MSPH) are unclear. Objective This study aims to investigate the associations of maternal/fetal SNPs of APOE, LPL, LDLR, PCSK9, and SCARB1 with the risk of MSPH and explore whether the maternal-fetal pairing pattern of the risk alleles can affect MSPH risk. Methods A nested case-control study was conducted that included 182 pregnant women with MSPH and 182 with maternal physiological hypercholesterolemia. Maternal venous and umbilical venous blood were collected to detect the SNPs of genes. The primary outcome was MSPH. Logistic regression model was used to determine the associations of SNPs with risk of MSPH. Results The C-allele in maternal APOE rs429358 T > C (adjusted odds ratio [OR] = 1.72, P = 0.033), G-allele in fetal APOE rs440446 C > G (adjusted OR = 1.62, P = 0.012) and T-allele in fetal LPL rs263 C > T (adjusted OR = 1.53, P = 0.011) increased the risk of MSPH. The A-allele in maternal LDLR rs7258950 G > A decreased the risk of MSPH (adjusted OR = 0.67, P = 0.028). For maternal-fetal pairing analysis, the variant concordance of PCSK9 rs2149041, rs7523141, rs7523242, rs7525649, and LDLR rs7258950 were associated with the decreased risk of MSPH under the dominant model. The variant concordance of other SNPs of PCSK9, APOE, LDLR, LPL, and SCARB1 were associated with the increased risk of MSPH. Conclusion This study supports the hypothesis that maternal and fetal genetic polymorphisms of lipid metabolic genes are associated with the risk of MSPH. The maternal-fetal variant concordance is also associated with this risk.

Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed populations were designated MHco3/18 or MHco18/3, where the lead isolate reflects the origin of the females. Three independent filial generations were generated for each cross, which were subjected to bioassays, molecular approaches and population genetic analyses to investigate the phenotypic and genotypic inheritance of benzimidazole (BZ) resistance at each stage. A panel of microsatellite markers confirmed the success of the genetic cross as markers from both parents were seen in the F1 crosses. Egg hatch tests revealed a stark difference between the two F1 crosses with ED50 estimates for MHco18/3 being 9 times greater than those for MHco3/18. Resistance factors based on ED50 estimates ranged from 6 to 57 fold in the filial progeny compared to MHco3(ISE) parents. Molecular analysis of the F167Y and F200Y SNP markers associated with BZ resistance were analysed by pyrosequencing and MiSeq deep amplicon sequencing, which showed that MHco3/18.F1 and MHco18/3.F1 both had similar frequencies of the F200Y resistant allele (45.3% and 44.3%, respectively), whereas for F167Y, MHco18/3.F1 had a two-fold greater frequency of the resistant-allele compared to MHco3/18.F1 (18.2% and 8.8%, respectively). Comparison between pyrosequencing and MiSeq amplicon sequencing revealed that the allele frequencies derived from both methods were concordant at codon 200 (rc = 0.97), but were less comparable for codon 167 (rc = 0.55). The use of controlled reciprocal genetic crosses have revealed a potential difference in BZ resistance phenotype dependent on whether the resistant allele is paternally or maternally inherited. These findings provide new insight and prompt further investigation into the inheritance of BZ resistance in H. contortus., Graphical abstract Image 1, Highlights • Reciprocal cross used to investigate benzimidazole (BZ) resistance. • Phenotypic and genotypic tools combined for analysis. • Inheritance of BZ resistance influenced by maternal &/or cytoplasmic mechanisms. • Double homozygous resistant genotypes at F167Y and F200Y detected on β−tubulin gene.

I. Background: Pistacia is kind of unisexual plant species that can take 4–5 years to initiate bearing stage of trees in terms of economic value. The fruits of species have an extreme importance in food, health and baking industry as a raw material. So, identify the individual in early juvenile period for pollination and position of trees is very crucial for growers. The objective of this study is developing markers for each Pistacia species which helps the screening the sex of plant seedling quickly before they reach reproduction stage without waiting morphological data. II. Methods and Results: Within the context, by using the power of KASP (Kompetitive Allele Specific PCR) assay technology as a marker screening system, we successfully discriminate 7 Pistacia species out of 8 which are P. atlantica, P. integerrima, P. khinjuk, P. mutica, P. terebinthus, P. vera and P. lentiscus. We have used a high-throughput DNA sequence read archive (SRA) to assemble a reference genome to use in our studies as de novo bioinformatics method. 4 genomic regions were sequenced with collected plant material from Antepfıstıgı Research Institute Collection Garden predominantly and 8 species were aligned intraspecifically for Single Nucleotide Polymorphism (SNP) mining. 12 SNP markers are converted to KASP markers and 5 of them (SNP-PIS-133396, SNP-PIS-167992, P-ATL-91951-565, P-INT-91951-256, P-KHI-91951-115) showed obvious allelic discrimination between male and female species. SNP-PIS-167992 and P-ATL-91951-565 were identified as best marker assays due to the allelic frequency differences in graphs which are apparent for all individuals and homozygosis/heterozygosis observed clearly. These markers could be most comprehensive for whole genus because the discriminability power of several species in once. III. Conclusions: As a conclusion, this study is reported first Pistacia gender discrimination by KASP, besides the precursor study for sex discrimination by KASP in plants.

Background: It is thought that genetic factors are influential in the etiology of polycystic ovarian syndrome (PCOS),the most frequent endocrinological disorder of females in their reproductive age. This study was carried out to elucidatethe association of rs13429458 and rs12478601 single nucleotide polymorphisms (SNPs) of the THADA gene andthe risk of the PCOS among a population of Iranian female patients.Materials and Methods: This case-control study contains 66 infertile women with PCOS (patient group) and 44healthy women without PCOS (control group) that referred to the IVF Unit of the Infertility Research Center of theAcademic Center for Education, Culture and Research (ACECR). The polymerase chain reaction (PCR) was utilizedto amplify genome DNA as well as direct sequencing to determine SNPs. The THADA rs12478601 and rs13429458genotypes were consequently examined with amplification refractory mutation system-PCR (ARMS-PCR).Results: In this study, we observed that rs13429458 polymorphism was not associated with PCOS risk in two groups (P=0.42). On the other hand, data analysis indicated that the rs12478601 genotype significantly increased the risk of PCOS in the case group (P=0.032) in compared with control group. We found that the “T” allele of rs12478601 in the THADA gene had a significant relation to PCOS in the case group (odds ratio [OR]: 2.574, 95% confidence interval [CI]: 1.439-4.604, P=0.001).Conclusion: This study has presented further evidence that TT and CT genotype of THADA rs12478601 is associatedwith a high risk of PCOS.

Objective Interleukin-1 (IL-1) is a pro-inflammatory cytokine which may be related to urolithiasis. Genetic polymorphisms of the interleukin-1β (IL-1β) have been proposed as markers for urolithiasis in some areas. Due to the high incidence of urolithiasis in Uighur children (Xinjiang, China) and existence of ethnic difference, our aim is to explore the potential of IL-1 gene polymorphisms and urolithiasis among these children. Methods Genomic DNA extracted from peripheral blood of 115 patients and 98 controls were used for genotype polymorphisms analyses. IL-1 receptor antagonist gene (IL-1RN) variable numbers of a tandem repeat (VNTR) gene polymorphisms were analyzed by PCR method. PCR-based restriction analysis was done for the IL-1β (−511) and IL-1β (+3954) gene polymorphisms by endonucleases Ava I and Taq I, respectively. The genotype distribution, allele frequencies, carriage rate and haplotype frequencies were statistically analyzed. Results No significant differences were observed in genotypic frequencies between pediatric urolithiasis patients and control group for IL-1RN gene (χ2 = 1.906, p = 0.605), IL-1β (−511) gene (χ2 = 0.105, p = 0.949), or IL-1β (+3954) gene (χ2 = 3.635, p = 0.169). There were yet no significant differences of the allele frequencies of IL-1RN VNTR gene (p = 0.779), IL-1β (-511) gene (p = 0.941), and IL-1β (+3954) gene (p = 0.418) in the case and control groups, as well as the carriage rate and haplotype of them (all p > 0.05). Conclusions The associations between IL-1RN VNTR, IL-1β (-511) and IL-1β (+3954) genes polymorphisms and urolithiasis were not significant in Uighur children. The results need to be confirmed in studies with larger population sample size, as well as in other ethnic groups.

The MMPs are endogenous proteolytic enzymes that require zinc and calcium as cofactors. MMP9 is one of the most complex matrix metalloproteinases in the gelatinase family and has many biological functions. In mammals, mmp9 is thought to be closely associated with cancer. However, studies in fish have rarely been reported. In this study, to understand the expression pattern of the ToMMP9 gene and its association with the resistance of Trachinotus ovatus to Cryptocaryon irritans, the sequence of the MMP9 gene was obtained from the genome database. The expression profiles were measured by qRT–PCR, the SNPs were screened by direct sequencing, and genotyping was performed. The ToMMP9 gene contained a 2058 bp ORF encoding a putative amino acid sequence of 685 residues. The homology of the ToMMP9 in teleosts was more than 85%, and the genome structure of ToMMP9 was conserved in chordates. The ToMMP9 gene was expressed in different tissues of healthy individuals and was highly expressed in the fin, the gill, the liver and the skin tissues. The ToMMP9 expression in the skin of the infected site and its adjacent sites increased significantly after C. irritans infection. Two SNPs were identified in the ToMMP9 gene, and the SNP (+400A/G) located in the first intron was found to be significantly associated with the susceptibility/resistance to C. irritans. These findings suggest that ToMMP9 may play an important role in the immune response of T. ovatus against C. irritans.

Studies focused solely on single organisms can fail to identify the networks underlying host–pathogen gene-for-gene interactions. Here, we integrate genetic analyses of rice (Oryza sativa, host) and rice blast fungus (Magnaporthe oryzae, pathogen) and uncover a new pathogen recognition specificity of the rice nucleotide-binding domain and leucine-rich repeat protein (NLR) immune receptor Pik, which mediates resistance to M. oryzae expressing the avirulence effector gene AVR-Pik. Rice Piks-1, encoded by an allele of Pik-1, recognizes a previously unidentified effector encoded by the M. oryzae avirulence gene AVR-Mgk1, which is found on a mini-chromosome. AVR-Mgk1 has no sequence similarity to known AVR-Pik effectors and is prone to deletion from the mini-chromosome mediated by repeated Inago2 retrotransposon sequences. AVR-Mgk1 is detected by Piks-1 and by other Pik-1 alleles known to recognize AVR-Pik effectors; recognition is mediated by AVR-Mgk1 binding to the integrated heavy metal-associated (HMA) domain of Piks-1 and other Pik-1 alleles. Our findings highlight how complex gene-for-gene interaction networks can be disentangled by applying forward genetics approaches simultaneously to the host and pathogen. We demonstrate dynamic coevolution between an NLR integrated domain and multiple families of effector proteins., ゲノム解読による植物病害抵抗性の解明 --イネ-いもち病菌「遺伝子対遺伝子」の戦い. 京都大学プレスリリース. 2023-02-01.

The transmembrane protein 18 (TMEM18) gene plays a central and peripheral role in weight regulation. TMEM18 genetic polymorphisms have been identified as an important risk factor for obesity, depending on ethnic population and age. This research aimed to study the association of common TMEM18 polymorphisms with obesity and their interactions with modifiable factors, namely drinking habits (sugar-sweetened beverages (SSBs), flavored water and wine) and physical activity (PA) in the Israeli population. Adults (n = 3089) were analyzed for common TMEM18 polymorphisms and lifestyle and nutrition habits were obtained from questionnaires using adjusted (age, sex) binary logistic regression models. TMEM18 rs939583 and rs1879523 were significantly associated with increased obesity risk (OR = 1.35, 95% CI (1.17–1.57) and OR = 1.66, 95% CI (1.29–2.15), respectively). TMEM18 rs939583 interacted with consumption of 1–3 weekly glasses of wine and PA to attenuate obesity risk (OR = 0.82 95% CI (0.74–0.9; p < 0.001) and OR = 0.74 95% CI (0.68–0.8), respectively), while physical inactivity, SSBs and flavored water consumption significantly enhanced obesity risk (OR = 1.54 95% CI (1.41–1.67), OR = 1.31 95% CI (1.14–1.51) and OR = 1.35 95% CI (1.13–1.62), respectively). PA duration was significantly associated with a lower BMI for rs939583 risk carriers, with a PA cutoff of >30 min/week (p = 0.005) and >90 min/week (p = 0.01). Common TMEM18 SNPs were significantly linked with adult obesity risk and interacted with modifiable lifestyle factors.

Purpose Breast cancer treatment is associated with adverse effects, which may delay return-to-work. Single nucleotide polymorphisms (SNPs) may influence the risk and severity of treatment toxicities, which in turn could delay return-to-work. We examined the association of 26 SNPs with return-to-work in premenopausal women with breast cancer. Methods Using Danish registries, we identified premenopausal women diagnosed with non-distant metastatic breast cancer during 2007‒2011, assigned adjuvant combination chemotherapy including cyclophosphamide and docetaxel. We genotyped 26 SNPs in 20 genes (ABCB1, ABCC2, ABCG2, CYP1A1, CYP1B1, CYP3A, CYP3A4, CYP3A5, GSTP1, SLCO1B1, SLCO1B3, ARHGEF10, EPHA4, EPHA5, EPHA6, EPHA8, ERCC1, ERCC2, FGD4 and TRPV1) using TaqMan assays. We computed the cumulative incidence of return-to-work (defined as 4 consecutive weeks of work) up to 10 years after surgery, treating death and retirement as competing events and fitted cause-specific Cox regression models to estimate crude hazard ratios (HRs) and 95% confidence intervals (CIs) of return-to-work. We also examined stable labor market attachment (defined as 12 consecutive weeks of work). Results We included 1,964 women. No associations were found for 25 SNPs. The cumulative incidence of return-to-work varied by CYP3A5 rs776746 genotype. From 6 months to 10 years after surgery, return-to-work increased from 25 to 94% in wildtypes (n = 1600), from 17 to 94% in heterozygotes (n = 249), and from 7 to 82% in homozygotes (n = 15). The HR showed delayed return-to-work in CYP3A5 rs776746 homozygotes throughout follow-up (0.48, 95% CI 0.26, 0.86), compared with wildtypes. Estimates were similar for stable labor market attachment. Conclusion Overall, the SNPs examined in the study did not influence return-to-work or stable labor market attachment after breast cancer in premenopausal women. Our findings did suggest that the outcomes were delayed in homozygote carriers of CYP3A5 rs776746, though the number of homozygotes was low.

Taste perception is a well-documented driving force in food selection, with variations in, e.g., taste receptor encoding and glucose transporter genes conferring differences in taste sensitivity and food intake. We explored the impact of maternal innate driving forces on sweet taste preference and intake and assessed whether their children differed in their intake of sweet foods or traits related to sweet intake. A total of 133 single nucleotide polymorphisms (SNPs) in genes reported to associate with eating preferences were sequenced from saliva-DNA from 187 mother-and-child pairs. Preference and intake of sweet-, bitter-, sour-, and umami-tasting foods were estimated from questionnaires. A total of 32 SNP variants associated with a preference for sweet taste or intake at a p-value < 0.05 in additive, dominant major, or dominant minor allele models, with two passing corrections for multiple testing (q < 0.05). These were rs7513755 in the TAS1R2 gene and rs34162196 in the OR10G3 gene. Having the T allele of rs34162196 was associated with higher sweet intake in mothers and their children, along with a higher BMI in mothers. Having the G allele of rs7513755 was associated with a higher preference for sweets in the mothers. The rs34162196 might be a candidate for a genetic score for sweet intake to complement self-reported intakes.

The codling moth is an economic pest of apple production in Croatia and has a cosmopolitan distribution. We have been working on CM biology, ecology, and genetics for over a decade to better understand how this pest has only changed its distribution, abundance, and movement patterns and what this means for improving control practices and management of the species in Croatia. Our initial work commenced with a study into the biology and ecology of CM under different treatments. Our findings showed that in the untreated orchard, two generations of CMs were observed per year, whereas an additional third flight period of the moths was observed in the treated orchards. This work was followed by a population genetic study which showed no genetic differentiation was found. Our most recent work on CM population genetics using SNPs found evidence that population sub-structuring may be occurring as a result of improved integrated control practices in Croatian apple orchids over the last decade. To further investigate population sub-structuring we investigated phenotypic traits under selection (ie. wings) using geometric morphometric (GM) methods. GM methods showed a reliable pattern of differences related to the type of control practice CM was subjected to. The combined use of SNPs and GM to detect resistant variants is a completely new approach and provides new insights into CM control. Recent innovative methods we’ve undertaken involve the use of structural engineering numerical modeling using the finite element method (FEM) to investigate the dispersal capabilities of CM in Croatia by modeling wing deformation against different wind speed moths experienced in the field. Our findings showed CM from the ecological orchards displayed the least wing deformation as the wind speed increased and had the most structurally sound wings compared to CM from integrated control orchids that had wings that were less structurally sound.

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in this study. We conducted a multi-phase study analysing 7,745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14,666 PDAC cases and 221,897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR=1.11, 95%CI=1.07-1.15, P=5.25×10-9 ). CDKN2B-AS1/ANRIL is a long non-coding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. This article is protected by copyright. All rights reserved.

Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/nu15040823/s1, Table S1: Hardy-Weinberg equilibrium; Table S2: Linkage disequilibrium; Table S3: Minor allele frequencies of SNPs; Table S4: Estimation of haplotype frequencies; Table S5: Polymorphisms and association with risk of asthma., Asthma is a chronic non-communicable disease that affects all age groups. The main challenge this condition poses is its heterogeneity. The role of vitamin D in asthma has aroused great interest, correlating low vitamin D levels and polymorphisms in the genes involved in its metabolic pathway with the risk of asthma. The aim of this study was to evaluate the influence of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolism on the susceptibility to asthma. An observational case-control study was performed, including 221 patients with asthma and 442 controls of Caucasian origin from southern Spain. The SNPs CYP24A1 (rs6068816, rs4809957), CYP27B1 (rs10877012, rs4646536, rs703842, rs3782130), GC (rs7041), CYP2R1 (rs10741657) and VDR (ApaI, BsmI, FokI, Cdx2, TaqI) were analyzed by real-time PCR, using TaqMan probes. The logistic regression model adjusted for body mass index revealed that in the genotype model, carriers of the Cdx2 rs11568820-AA genotype were associated with a higher risk of developing asthma (p = 0.005; OR = 2.73; 95% CI = 1.36–5.67; AA vs. GG). This association was maintained in the recessive model (p = 0.004). The haplotype analysis revealed an association between the ACTATGG haplotype and higher risk of asthma for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130 and rs10877012 genetic polymorphisms (p = 0.039). The other SNPs showed no effect on risk of developing asthma. The Cdx2 polymorphism was significantly associated with the susceptibility of asthma and could substantially act as a predictive biomarker of the disease., ERDF funds (EU) from the Instituto de Salud Carlos III (PT13/0010/0039) supported by co-funding grants from the Biobank of the Hospital Universitario Virgen de las Nieves

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations. OBJECTIVES: Determine associations of demographic, clinical, laboratory, and single nucleotide polymorphisms in the ACE2, TMPRSS2, TNF-α, and IFN-γ genes to the incidence of infection and mortality in COVID-19 patients. DESIGN: Prospective cohort study SETTINGS: Various cities in the Kurdistan Region of Iraq. PATIENTS AND METHODS: This prospective cohort study compared laboratory markers (D-dimer, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], C-reactive protein [CRP], lymphocyte and neutrophil counts) between COVID-19 patients and healthy controls. DNA was extracted from blood, and genotypes were done by Sanger sequencing. MAIN OUTCOME MEASURES: Single nucleotide polymorphisms of the ACE2, TMPRSS2, TNF-α, and IFN-γ genes and demographic characteristics and laboratory markers for predicting mortality in COVID-19. SAMPLE SIZE: 203 (153 COVID-19 patients, 50 health control subjects). RESULTS: Forty-eight (31.4%) of the COVID-19 patients died. Age over 40 and comorbidities were risk factors for mortality, but the strongest associations were with serum IFN-γ, the neutrophil-to-lymphocyte ratio (NLR), and serum TNF-α. The AA genotype and A allele of TMPRSS2 rs2070788 decreased while the GA genotype and A allele of TNF-α increased susceptibility to COVID-19. Patients with the GA genotype of TNF-α rs1800629 had shorter survival times (9.9 days) than those carrying the GG genotype (18.3 days) (P

Escaped farmed Atlantic salmon represent a well-documented and ongoing threat to wild conspecific populations. In Norway, the world-leading producer of farmed salmon, annual monitoring of straying and genetic introgression by farmed escapees in wild salmon rivers has been carried out since the late 1980s. In this study, we applied molecular and statistical methods routinely used in the Norwegian monitoring programme to investigate the magnitude of escaped farmed salmon and genetic introgression in salmon rivers on the west coast of Sweden, where suspected escapees have been observed. Our results confirm that escaped farmed salmon stray, successfully spawn, and produce offspring at levels similar to those observed in neighbouring Norway. These findings raise concerns over population productivity and long-term viability and highlight the need for more permanent monitoring of the presence and consequences of escaped farmed salmon in Swedish salmon rivers. Our results further illustrate that farmed gene flow may constitute a transboundary problem with potential international implications. Gene flow · Aquaculture · Atlantic salmon · Salmo salar · Single nucleotide polymorphisms · SNPs

Hybridization is a natural process at species‐range boundaries that may variably promote the speciation process or break down species barriers but minimally will influence management outcomes of distinct populations. White‐tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) have broad and overlapping distributions in North America and a recognized capacity for interspecific hybridization. In response to contemporary environmental change to any of one or multiple still‐unknown factors, mule deer range is contracting westward accompanied by a westward expansion of white‐tailed deer, leading to increasing interactions, opportunities for gene flow, and associated conservation implications. To quantify genetic diversity, phylogenomic structure, and dynamics of hybridization in sympatric populations of white‐tailed and mule deer, we used mitochondrial cytochrome b data coupled with SNP loci discovered with double‐digest restriction site‐associated DNA sequencing. We recovered 25,018 SNPs across 92 deer samples from both species, collected from two regions of western Kansas. Eight individuals with unambiguous external morphology representing both species were of hybrid origin (8.7%), and represented the product of multi‐generational backcrossing. Mitochondrial data showed both ancient and recent directional discordance with morphological species assignments, reflecting a legacy of mule deer males mating with white‐tailed deer females. Mule deer had lower genetic diversity than white‐tailed deer, and both mitochondrial and nuclear data suggest contemporary mule deer effective population decline. Landscape genetic analyses show relative isolation between the two study regions for white‐tailed deer, but greater connectivity among mule deer, with predominant movement from north to south. Collectively, our results suggest a long history of gene flow between these species in the Great Plains and hint at evolutionary processes that purge incompatible functional genomic elements as a result of hybridization. Surviving hybrids evidently may be reproductive, but with unknown consequences for the future integrity of these species, population trajectories, or relative susceptibility to emerging pathogens.

Introduction: Coronary Artery Disease (CAD) is a leading cause of death in most countries as well as developing countries like India and incidence of susceptibility to CAD is associated with increased frequencies of particular Single Nucleotide Polymorphisms (SNPs) located in Lipoprotein Lipase (LPL) gene. Aim: To evaluate the association of LPL gene polymorphisms variation namely LPL-HindIII, LPL-PvuII and LPL-Ser447Ter with CAD in Bengali population by Polymerase Chain Reaction (PCR) based Restriction Fragment Length Polymorphism (RFLP). Materials and Methods: A retrospective case-control study was conducted at RG Kar Medical College and Hospital, Kolkata, West Bengal, India from April 2016 to October 2016. The study included 100 patients suffering from CAD and 100 controls from healthy populations were taken and Deoxyribonucleic Acid (DNA) extraction followed by genotyping was done by PCR based RFLP study. Hardy-Weinberg equilibrium for genotypic frequencies were analysed followed by goodness-of-fit Chisquare (χ2 ) test to check the equilibrium of the SNP alleles. Results: Total 100 patients, 57 males and 43 females with mean age 61.42±9.34 years suffering from CAD were cases and 100 patients were controls, 61 males and 39 females with mean age 49.37±10.21 years. It was found that genotypic frequencies for HindIII, PvuII and MnlI polymorphism of LPL gene were not deviated from the Hardy-Weinberg expectations in both control and cases groups. We could not find any significant association of the HindIII, PvuII and Ser447Ter polymorphisms of the LPL gene with occurrence of CAD in target population after appropriate data analysis using SPSS and MedCalc software. Conclusion: Association and prediction of susceptibility patterns in ethnic population may require a prospective study involving higher number of cases which subsequently leads to possible pharmacogenomic utility on a broader perspective. Although authors did not get any statistically significant association between CAD and the genes of interest but these findings would lead to a better understanding of the condition and open up more avenues for study, treatment and prevention of CAD.

Background Toll-like (TLRs) play a crucial role in both adaptive and innate immunity. The aim of the present study was to assess the association of TLR5-rs5744168, TLR9-rs187084, and TLR9-rs352140 single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) in Egyptian patients. Results The C allele and homozygous CC genotype of the TLR9-rs352140 in co-dominant and recessive models were more prevalent in SLE patients than controls (P = 0.047, P = 0.017, and P = 0.005 respectively). In contrast, allelic and genotyping distribution of TLR5-rs5744168 and TLR9-rs187084 SNPs showed no association with the risk of SLE. The T allele of the TLR5-rs5744168 was more prevalent in LN patients than controls (P = 0.021). The homozygous TT genotype of TLR5-rs5744168 SNP was more prevalent in LN patients in the co-dominant and the recessive models than controls (P = 0.036 and P = 0.011 respectively). The C allele of the TLR9-rs352140 was more prevalent in LN patients than controls (P = 0.015). The homozygous CC genotype of the TLR9-rs352140 SNP was more prevalent in LN than controls in co-dominant and recessive models (P = 0.002 and P < 0.001). In the recessive model of the TLR5-rs5744168 SNP, the TT genotype was found in 3.2% of the SLE patients while none of the SLE patients without LN or controls had TT genotype (P = 0.036). Also, in the recessive model of the TLR9-rs352140 SNP, the CC genotype was significantly more frequent in SLE patients with LN than without LN (44.4% vs 29.9%, P = 0.045). Conclusion Our results support the potential role of TLR5-rs5744168 SNP and TLR9-rs3532140 SNP not only in increasing the risk for development of SLE, but also in increasing the risk of LN in SLE patients among the Egyptian population.

Ahmad H Mufti, 1 Imad A AlJahdali, 2 Nasser A Elhawary, 1 Samar N Ekram, 1 Iman Abumansour, 1 Ikhlas A Sindi, 3 Hind Naffadi, 4 Ezzeldin N Elhawary, 5 Najiah M Alyamani, 6 Ghydda Alghamdi, 1 Wafaa Alosaimi, 7 Ghufran Rawas, 8 Amaal Alharbi, 9 Mohammed T Tayeb 1 1Department of Medical Genetics, College of Medicine, Umm Al-Qura University, Mecca, 21955, Saudi Arabia; 2Department of Community Medicine, College of Medicine, Umm Al-Qura University, Mecca, 21955, Saudi Arabia; 3Department of Biotechnology, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 4Common Science, First Year Deanship, Umm Al-Qura University, Mecca, Saudi Arabia; 5MS Genomic Medicine Program, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK; 6Department of Biology, College of Jeddah, Jeddah, Saudi Arabia; 7Department of Hematology, Maternity and Children Hospital, Mecca, Saudi Arabia; 8King Abdullah Medical City, Mecca, Saudi Arabia; 9Saudi Biobank National ProjectKing Abdullah International Medical Research Center, Jeddah, Saudi ArabiaCorrespondence: Nasser A ElhawaryDepartment of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi ArabiaTel +966 55 369 2180Email naelhawary@uqu.edu.saBackground: The antigen processing 1 (TAP1) and proteasome 20S subunit beta 9 (PSMB9) genes are associated with strong susceptibility to many autoimmune diseases. Here, we explored whether TAP1/PSMB9 genetic variants, individually or combined, affected susceptibility to the complex, autoimmune-based skin disorder vitiligo.Methods: Samples of genomic DNA from buccal cells of 172 patients with vitiligo and 129 healthy controls were analyzed using TaqMan™ genotyping assays for the TAP1 rs1135216 (A>G) and PSMB9 rs17587 (A>G) single nucleotide polymorphisms (SNPs). SNPStats software (https://www.snpstats.net) was utilized to choose the best interactive inheritance mode for selected SNPs.Results: The genotype frequencies for the TAP1 rs1135216 and PSMB9 rs17587 SNPs were in Hardy–Weinberg equilibrium for cases (P= 0.11 and P= 0.10, respectively) but not for controls (P< 0.05). The TAP1 rs1135216 (D637G) and PSMB9 rs17587 (R60H) SNPs increased the risk of vitiligo four-fold and two-fold, respectively (odds ratio [OR]= 4.6; 95% confidence interval [CI], 3.2– 6.5; P< 0.0001 and OR= 2.2; 95% CI, 1.5– 3.1; P< 0.0001). The recessive model (G/G-D/G versus D/D) and the codominant model (R/R versus R/H) were the best models of inheritance for the rs113526 and rs17587 SNPs, respectively (OR= 16.4; 95% CI, 2.0– 138; P= 0.0006 and OR= 1.7; 95% CI, 0.3– 1.8; P= 0.013). Vulgaris, focal vulgaris, and acryl/acrofacial were the most common vitiligo subtypes in our sample (51%, 21%, and 19%, respectively). Heterozygous rs113526 (637D/G) and rs17587 (60R/H) were the most common genotypes in most vitiligo subtypes. The heterozygous 637D/G genotype and the 637G variant allele were significantly more common in patients with active disease than in patients with stable disease (P= 0.000052 and P= 0.0063, respectively).Conclusion: Our findings suggest a crucial role for TAP1 rs1135216 and PSMB9 rs17587 in the risk and progression of vitiligo in the Saudi community. Genomic analyses are needed to identify more candidate genes and more genetic variants associated with vitiligo.Keywords: vitiligo, TAP1/PSMB9, single nucleotide polymorphisms, TaqMan genotyping, linkage disequilibrium

5-fluorouracil (5-FU) and its pro-drug capecitabine are widely used anticancer agents. Most 5-FU catabolism is dependent on dihydropyrimidine dehydrogenase (DPD) encoded by the DPYD gene, and DPYD variants that reduce DPD function increase 5-FU toxicity. Most DPD deficient patients are heterozygous and can be treated with reduced 5-FU dosing. We describe a patient with a genotype associated with near complete absence of DPD function, and severe and likely fatal toxicity with 5-FU treatment. The patient was treated effectively with alternative systemic therapy. Routine pretreatment DPYD genotyping is recommended by the European Medicines Agency, and guidelines for use of 5-FU in DPD deficient patients are available. However, outside the province of Quebec, routine pretreatment screening for DPD deficiency remains unavailable in Canada. It is likely our patient would have died from 5-FU toxicity under the current standard of care, but instead provides an example of the potential benefit of DPYD screening on patient outcomes.

Hybrid zones between diverged lineages offer an unique opportunity to study evolutionary processes related to speciation. Natural and anthropogenic hybridization in the black basses (Micropterus spp.) is well documented, including an extensive intergrade zone between the widespread northern Largemouth Bass (M. salmoides) and the Florida Bass (M. floridanus). Phenotypic surveys have identified an estuarine population of Largemouth Bass (M. salmoides) in the Mobile-Tensaw Delta, with larger relative weight and smaller adult size compared to inland populations, suggesting a potential third lineage of largemouth bass. To determine the evolutionary relationships between these Mobile Delta bass populations, M. salmoides, and M. floridanus, putative pure and intergrade populations of all three groups were sampled across the eastern United States. Phylogenetic analyses of 8,582 nuclear SNPs derived from genotype-by-sequencing and the ND2 mitochondrial gene determined that Delta bass populations stem from a recently diverged lineage of Largemouth Bass. Using a novel quantitative pipeline, a panel of 73 diagnostic SNPs was developed for the three lineages, evaluated for accuracy, and then used to screen 881 samples from 52 sites for genetic integrity and hybridization on the Agena MassARRAY platform. These results strongly support a redrawing of native ranges for both the intergrade zone and M. floridanus, which has significant implications for current fisheries management. Furthermore, Delta bass ancestry was shown to contribute significantly to the previously described intergrade zone between northern Largemouth Bass and Florida Bass, suggesting a more complex pattern of secondary contact and introgression among these diverged Micropterus lineages.

Purpose: Cytarabine arabinoside (Ara-C) is an anti-metabolite that is commonly used as a therapeutic agent for acute leukemia; however, it can cause adverse drug reactions, such as digestive disorders, rashes, and fever. Therefore, identification of gene markers that can accurately predict the development of adverse drug reactions is useful for selecting effective drugs for therapy. After entering the cells, Ara-C is metabolized to Ara-C triphosphate, which inhibits DNA synthesis and exhibits antitumor activity. Therefore, we conducted an association study between the adverse reactions to cytarabine therapy and single nucleotide polymorphisms (SNPs) in cytarabine metabolic genes. Methods: Among the patients treated with cytarabine at the Department of Hematology at Tokushima University Hospital, 46 patients provided informed consent and were included in this study. We selected 14 tag SNPs located in nine genes that are involved in the cytarabine metabolic pathway; these SNPs were genotyped using the polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) technique. Association analyses between adverse reactions to Ara-C therapy and SNPs were performed using logistic regression analysis. Results: The rs9394992 polymorphism in the SLC29A1 gene and rs3886768 polymorphism in the DCTD gene were associated with the development of rash after Ara-C therapy. The rs7277 polymorphism in the DCTD gene was associated with fever, and the rs16945930 polymorphism in the ABCC11 gene was associated with sore throat. Conclusions: Our findings suggest that SNPs in the Ara-C metabolic genes influence the development of adverse reactions to Ara-C, and the results suggest that these genes can be predictive of adverse reactions to Ara-C therapy.

Sulfur plays a vital role in the primary and secondary metabolism of plants, and carries an important function in a large number of different compounds. Despite this importance, compared to other mineral nutrients, relatively little is known about sulfur sensing and signalling, as well as about the mechanisms controlling sulfur metabolism and homeostasis. Sulfur contents in plants vary largely not only among different species, but also among accessions of the same species. We previously used associative transcriptomics to identify several genes potentially controlling variation in sulfate content in the leaves of Brassica napus, including an OASC gene for mitochondrial O-acetylserine thiollyase (OAS-TL), an enzyme involved in cysteine synthesis. Here, we show that loss of OASC in Arabidopsis thaliana lowers not only sulfate, but also glutathione levels in the leaves. The reduced accumulation is caused by lower sulfate uptake and translocation to the shoots; however, the flux through the pathway is not affected. In addition, we identified a single nucleotide polymorphism in the OASC gene among A. thaliana accessions that is linked to variation in sulfate content. Both genetic and transgenic complementation confirmed that the exchange of arginine at position 81 for lysine in numerous accessions resulted in a less active OASC and a lower sulfate content in the leaves. The mitochondrial isoform of OAS-TL is, thus, after the ATPS1 isoform of sulfurylase and the APR2 form of APS reductase 2, the next metabolic enzyme with a role in regulation of sulfate content in Arabidopsis.

International audience; Background: Unraveling the genetic background in a significant proportion of patients with both sporadic and familial IPF provided new insights into the pathogenic pathways of pulmonary fibrosis. Aim: The aim of the present study is to overview the clinical significance of genetics in IPF. Perspective: It is fascinating to realize the so-far underestimated but dynamically increasing impact that genetics has on aspects related to the pathophysiology, accurate and early diagnosis, and treatment and prevention of this devastating disease. Genetics in IPF have contributed as no other in unchaining the disease from the dogma of a “a sporadic entity of the elderly, limited to the lungs” and allowed all scientists, but mostly clinicians, all over the world to consider its many aspects and “faces” in all age groups, including its co-existence with several extra pulmonary conditions from cutaneous albinism to bone-marrow and liver failure. Conclusion: By providing additional evidence for unsuspected characteristics such as immunodeficiency, impaired mucus, and surfactant and telomere maintenance that very often co-exist through the interaction of common and rare genetic variants in the same patient, genetics have created a generous and pluralistic yet unifying platform that could lead to the understanding of the injurious and pro-fibrotic effects of many seemingly unrelated extrinsic and intrinsic offending factors. The same platform constantly instructs us about our limitations as well as about the heritability, the knowledge and the wisdom that is still missing.

The renin-angiotensin system (RAS), besides being a major regulator of blood pressure, is also involved in tumor angiogenesis. Emerging evidence suggests a correlation between the use of pharmacologic RAS inhibitors and a delay in urothelial bladder cancer (BC) progression. However, it is unknown whether RAS gene variants may predispose to the development of BC. This study examined the association of RAS single nucleotide polymorphisms (SNPs) including AT1R rs5186, AT2R rs11091046, REN rs12750834, ANG rs4762, and ANG rs699 with the risk of developing non-invasive BC. Peripheral blood samples from 73 patients with T1 urothelial BC (66 men, seven women) and an equal number of healthy subjects (control group) were collected. The TT genotype of the REN rs12750834 SNP (OR: 2.8 [1.3–6.05], p = 0.008) and to a lesser extent the presence of the T allele (OR: 2.3 [1.2–4.48], p = 0.01) conferred a higher risk of BC. The highest risk for BC within SNP carriers of the RAS system was associated with the presence of the CC genotype (OR: 17.6 [7.5–41.35], p &lt, 0.001) and C allele (OR: 17.7 [8.8–35.9], p &lt, 0.001) of the ANG rs699 SNP. The presence of the AT2R rs11091046 SNP, particularly the AA genotype, was associated with a protective effect against developing BC (OR: 0.268 [0.126–057], p &lt, 0.001). In conclusion, these results support the clinical utility of RAS gene SNPs AT2R rs11091046, REN rs12750834, and ANG rs699 in the genetic cancer risk assessment of patients and families with BC.

Introduction Non-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population, Objective The aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients. Methods In this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case–control and family-based associations were analyzed. Results The case–control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and non-syndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01–4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34–11.54). In addition, we did not detect any transmission-disequilibrium in rs7078160 (p = 0.68). Conclusion This study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.

The study was conducted to search for polymorphisms located in the 10th chromosome associated with colorectal adenocarcinoma in representatives of the Kazakhstan population. Study was performed with 282 colorectal cancer (CRC) patients and 159 controls. Genotyping of SNPs was performed by QuantStudio 12K Flex PCR. For four significant SNPs inheritance model analysis was performed. Increasing risk of CRC was noted for rs10795668 in log-additive model (OR = 1.45, 95% CI: 1.05–1.99, p = 0.023); for rs1035209 in log-additive model (OR = 1.79, 95% CI: 1.18–2.72, p = 0.003); for rs11190164 in log-additive model (OR = 1.67, 95% CI: 1.17–2.38, p = 0.004). Decreasing risk of CRC was noted for rs10506868 in log-additive model (OR = 0.56, 95% CI: 0.37–0.85, p = 0.006). We detected SNPs that are associated with CRC risk in the Kazakhstan population.

s Background Diabetic retinopathy (DR) is one of the most common chronic microvascular complications of diabetes. Many studies have suggested that genetic factors are important in the context of DR. This study evaluated the associations of GWAS (Genome-wide association study) -identified DR-associated SNPs in a Chinese population in Guangxi Province with type 2 diabetes mellitus (T2DM). Methods A total of 386 hospitalized T2DM patients without proliferative diabetic retinopathy (PDR) and 316 hospitalized T2DM patients with PDR were included in this case–control study. Four tag SNPs, including rs1800896 in the IL-10 gene, rs2010963 in the VEGFA gene, rs2070600 in the RAGE gene and rs2910164 in the miR-146a gene, were examined using KASP (kompetitive allele specific PCR) genotyping assays. Results There were no significant differences in the genotype or allele frequencies of the miR-146a polymorphism (rs2910164) between subjects with PDR and those without DR. The TC genotype of rs1800896 was determined to be associated with an increased risk of PDR (the odds ratio (OR) was 2.366, with a 95% confidence interval (CI) ranging from 1.144 to 4.894). The CG genotypes of rs2010963 was associated with an decreased risk of PDR (the OR was 0.588, with a 95% CI ranging from 0.366 to 0.946). Regarding rs2070600, 2 genotypes (TT and CT) were associated with a decreased risk of PDR (the OR of the TT genotype was 0.180, with a 95% CI ranging from 0.037 to 0.872, and the OR of the CT genotype was 0.448, with a 95% CI ranging from 0.266 to 0.753). Conclusions The rs1800896 polymorphisms in the IL-10 gene, rs2010963 in the VEGFA gene and rs2070600 in the RAGE gene are associated with the risk of PDR in the Han Chinese population of Guangxi Province. Our findings provide suggestive evidence that these polymorphisms may be involved in the pathogenesis of PDR and should be investigated further.

Gohar Tsakanova,1,2 Ani Stepanyan,1 Rudi Steffensen,3 Armine Soghoyan,4 Jens Christian Jensenius,5 Arsen Arakelyan1 1Institute of Molecular Biology NAS RA, Yerevan, Armenia; 2CANDLE Synchrotron Research Institute, Yerevan, Armenia; 3Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark; 4“Surb Grigor Lusavorich” Medical Center CJSC, Yerevan, Armenia; 5Department of Biomedicine, Aarhus University, Aarhus, DenmarkCorrespondence: Gohar TsakanovaInstitute of Molecular Biology NAS RA, 7 Hasratyan Street, Yerevan, 0014, ArmeniaTel +374 94 123070Fax +374 10 282061Email g_tsakanova@mb.sci.amPurpose: The current study aimed to investigate in an Armenian population the levels of pattern recognition molecules (PRMs) of lectin complement pathway (LCP), MBL (mannan-binding lectin) and M-ficolin in plasma in ischemic stroke (IS), and the possible association of 11 single nucleotide polymorphisms (SNPs) in MBL2, FCN1 and FCN2 genes.Patients and Methods: A total of 122 patients with IS and 150 control subjects were included in this study. Immunofluorometric assays (TRIFMAs) and real-time polymerase chain reactions with TaqMan probes were conducted.Results: According to the results, the levels of M-ficolin in IS patients are significantly higher than in control subjects, and the MBL2 rs11003125 and rs12780112 SNPs, as well as MBL2 rs12780112&ast;T and FCN1 rs10120023&ast;T minor alleles (MAs) are negatively associated with the risk of IS. Further, MBL2 rs11003125 and rs1800450 SNPs and the carriage of their MAs, as well as FCN1 rs2989727 SNP and the carriage of FCN1 rs10120023&ast;T MA significantly alter plasma MBL and M-ficolin levels in IS patients, respectively. Five common haplotypes in MBL2 gene and three common haplotypes in FCN1 and FCN2 genes were revealed, among which CGTC was negatively associated with IS and decreasing MBL plasma levels in IS.Conclusion: In conclusion, we suggest that LCP PRMs are associated with the risk of developing IS, and may also participate in pathological events leading to post-ischemic brain damage. This study emphasizes the important contribution of alterations of LCP PRMs on genomic and proteomic levels to the pathomechanisms of ischemic stroke, at least in an Armenian population.Keywords: human ischemic stroke, humoral pattern recognition molecules, lectin complement pathway, single nucleotide polymorphisms, haplotypes

Xi Zhang,1 Ziming Wan,1 Si Cheng,2 Hua Gan1 1Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Hua GanDepartment of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaEmail correspondzx@126.comIntroduction: ENPP1 and ENTPD1 are two main enzymes involved in ATP-AMP-ADP-adenosine axis, which is associated with lipid metabolism, diabetes mellitus (DM) and renal fibrosis. The single nucleotide polymorphisms (SNPs) of ENPP1 and ENTPD1, rs1044498 and rs6584026, are associated with these factors. This retrospective study aimed to address the two SNPs variants in hemodialysis (HD) patients and analyzes their relations with clinical characteristics.Methods: This study included 543 regular HD patients over 3 months at our center. Overnight fasting peripheral blood sample was taken from each subject to extract the DNA. The genotypes of rs1044498 and rs6584026 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The basic clinical data were noted such as sex, age, and HD-age, and the main causes of chronic kidney disease (CKD) and the clinical characteristics were collected on average at least three times in half a year. T-test and Chi-test were performed for the statistical analyses. Binary logistic regression was applied for the significant parameters by excluding the confounders, gender, age and HD-age. All statistical tests were considered significant for P< 0.05.Results: The rs1044498 genotypes showed in two types, A/A and A/C without C/C. The rs6584026 genotypes were C/C and C/T without T/T. The genotype frequency of rs1044498 (A/C) was 0.238, and the genotype frequency of rs6584026 (C/T) was 0.328. The age and the level of lipoprotein α showed statistical significance with rs1044498 variant (A/C, P< 0.05). The rs6584026 variant (C/T) was frequently found in patients with nephritis (P< 0.05). The albumin, alkaline phosphatase (ALP), lipoprotein α, cholesterol, apolipoprotein B (Apo B), Apo B/A1 and nephritis were independently associated with rs6584026 variant (C/T, P< 0.05) in binary logistic regression model by controlling the confounders of gender, age and HD-age. High level of triglyceride and low level of urine nitrogen were related to rs6584026 variant (C/T, P< 0.05).Conclusion: The rs1044498 and rs6584026 SNPs were related to several high levels of lipids, and rs6584026 variant was related to nephritis and autoimmune disease. The rs6584026 SNP may contribute to the increased risks of cholesterol and ApoB/A1 in HD patients.Keywords: chronic kidney disease, CKD, single nucleotide polymorphisms, SNPs, ectonucleotide pyrophosphatase/phosphodiesterase 1, ENPP1, ectonucleoside triphosphate diphosphohydrolase 1, ENTPD1, rs1044498, rs6584026