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Aim: To explore the potential association between the KLF14 rs4731702 polymorphism and metabolic syndrome traits among patients diagnosed with type 1 diabetes (T1D). Methods: The study group included 350 patients with T1D and 250 healthy control subjects. The analysis focused on the genotyping of KLF14 rs4731702 single nucleotide polymorphism (SNP), as well as evaluating serum concentrations of inflammatory markers, blood pressure, lipid profiles, and the quantitative status of CD4 + CD25highFOXP3+ T cells. Results: Patients with T1D carrying the T allele of KLF14 rs4731702 SNP had higher high‐density lipoprotein cholesterol, lower low‐density lipoprotein cholesterol, as well as lower glycated haemoglobin and serum concentration of proinflammatory markers than C allele carriers. They also developed hypertension less often than carriers of the C allele. The analysis of CD4 + CD25highFOXP3+ regulatory T‐cell status based on KLF14 genotype showed that, in T1D patients, those with the TT genotype had the highest frequency of these cells compared to carriers of the CC and CT genotypes. Conclusion: Our study suggests that the T allele of the KLF14 rs4731702 SNP might confer a protective effect against the development of obesity, hypertension, dyslipidaemia, and chronic inflammatory state in patients diagnosed with T1D. [ABSTRACT FROM AUTHOR]

Purpose: Primaquine (PQ) is recommended for radical cure of Plasmodium vivax (Pv) malaria, but its utilization is still limited due to high risk of severe haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-d). The aim of the present study is to assess the different genotypic variants leading to G6PD-d in Delhi and Goa regions of India. Methods: A total of 46 samples (34 retrospective Pv-mono-infected samples and 12 Pv-uninfected samples) were included in the study. Various genetic variants leading to G6PD-d were analysed by PCR amplification and DNA sequencing of different targeted exons of G6PD gene. Results: Molecular analysis showed presence of four mutations in study population viz. 1311 C > T, 34.1% & IVSXI 93T > C, 45.5% and two novel mutations 1388G > T, 2.3% and 1398 C > T, 2.3% (silent mutation). The bioinformatics and computational analysis demonstrate that the slight conformational changes caused by R643L mutation in protein are deleterious in nature. Conclusion: The observed mutations do not clarify the role or association between G6PD-d and Pv-infected cases. Further investigation is required in order to fully comprehend and analyse the precise role of these mutations with context to malaria infections. [ABSTRACT FROM AUTHOR]

The CUBN gene polymorphisms have been implicated in the pathogenesis of diabetes mellitus, encompassing both type 1 diabetes and type 2 diabetes. Nevertheless, the outcomes have been erratic. We conducted a comprehensive review to examine the connections. The literature was obtained from PubMed, ISI Web of Science, EmBase, and Scopus databases. The systematic review of the relationships between CUBN gene polymorphisms and diabetes risk identified 8 studies based on the search technique and inclusion criteria. Every single study that was considered used a casecontrol methodology. There was no study that was not considered to be of "high" or "medium" quality. The CUBN gene polymorphism in type 2 diabetes was the subject of five investigations involving 54,0970 patients and 435,312 controls. The CUBN gene polymorphism in type 1 diabetes was the subject of three studies including 19,660 patients and 388,374 controls. The majority of the research were conducted in European communities, with one study specifically focusing on American groups. Finally, the investigations varied in the platform utilized for genotyping or sequencing. While the study uncovers a new connection between the CUBN gene polymorphism and type 1 diabetes, the specific mechanism by which this polymorphism increases the chance of developing diabetes requires additional exploration. The results offer fresh perspectives on the genetic structure of albuminuria and emphasize specific genes and pathways that can be targeted to prevent kidney damage associated with type 2 diabetes. Our findings suggest that the CUBN gene may play a significant role in the genetic vulnerability to diabetes in individuals of European and American descent. Nevertheless, the generalizability of these findings to other ethnic groups remains unknown due to the previously documented significant variations in the genetic structure of CUBN gene between European and African populations. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. Methods: Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. Results: The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017–5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073–5.396, P = 0.033). Conclusions: NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS. [ABSTRACT FROM AUTHOR]

Introduction: Alveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage of Echinococcus multilocularis. Domestic animals, dogs, foxes, and small mammals constitute the circular chain of AE. To evaluate the infection, distribution, and genetic polymorphism of AE in the Ili Prefecture (Nilka, Xinyuan and Zhaosu), we conducted this survey. Methods: In June and July 2018, 267 small mammals were captured using waterinfusion and mousetrap methods. Combined pathogenic and molecular biological methods were used to observe the histopathology of Echinococcus carried by rodents, amplify the mitochondrial nad1 gene of the pathogen, and investigate the genotype and haplotype diversity of Echinococcus in rodents in Ili Prefecture. Results: Morphological identification revealed that these captured small mammals belonged to three species, with Microtus gregalis being the dominant species (183/267). Pathological and molecular biological results confirmed that E. multilocularis was the pathogen of echinococcosis in small mammals, with an infection rate of 15.73% (42/267). Among the three areas sampled, the highest infection rate of rodents was 25.45% (14/55) in Nilka County. However, there was no significant difference in the infection rates between regions (χ² = 5.119, p > 0.05). Of the three captured rodent species, M. gregalis had the highest infection rate of 17.49% (32/183), but there was no significant difference in infection rates between the rodent species (χ² = 1.364, p > 0.05). Phylogenetic analyses showed that the nad1 gene sequences obtained in this study clustered in the same clade as isolates from China. These isolates contained 21 haplotypes (Hap_1-21); Hap_2 was the most common haplotype (9/42). Furthermore, haplotype diversity (0.925 ± 0.027) and nucleotide diversity (0.01139 ± 0.00119) were higher in the Ili Prefecture than in other regions, indicating that population differentiation was high. Tajima's D and Fu's Fs tests were negative (p > 0.10), indicating that the population had expanded. The low fixation index (Fst) ranged from 0.00000 to 0.16945, indicating that the degree of genetic differentiation was different among different populations. Discussion: In summary, Ili Prefecture is a high incidence area of AE, and Microtus spp. may play an important role in the transmission of AE in this area. The results of this study provide basic data for further study of the molecular epidemiology, genetic differences, and control of E. multilocularis in the Ili Prefecture, Xinjiang. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental disorders (NDDs) like intellectual disability (ID) are highly heritable, but the environment plays an important role. For example, endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and its analogues, have been termed neuroendocrine disruptors. This study aimed to evaluate the influence of different genetic polymorphisms (SNPs) on cognitive function in Spanish schoolchildren according to dietary bisphenol exposure. Methods: A total of 102 children aged 6–12 years old were included. Ten SNPs in genes involved in brain development, synaptic plasticity, and neurotransmission (BDNF, NTRK2, HTR2A, MTHFR, OXTR, SLC6A2, and SNAP25) were genotyped. Then, dietary exposure to bisphenols (BPA plus BPS) was estimated and cognitive functions were assessed using the WISC-V Spanish form. Results: BDNF rs11030101-T and SNAP25 rs363039-A allele carriers scored better on the fluid reasoning domain, except for those inheriting the BDNF rs6265-A allele, who had lower scores. Secondly, relevant SNP–bisphenol interactions existed in verbal comprehension (NTRK2 rs10868235 (p-int = 0.043)), working memory (HTR2A rs7997012 (p-int = 0.002), MTHFR rs1801133 (p-int = 0.026), and OXTR rs53576 (p-int = 0.030)) and fluid reasoning (SLC6A2 rs998424 (p-int = 0.004)). Conclusions: Our findings provide the first proof that exploring the synergistic or additive effects between genetic variability and bisphenol exposure on cognitive function could lead to a better understanding of the multifactorial and polygenic aetiology of NDDs. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Sunitinib exhibits considerable interindividual variability in exposure. While the target total plasma concentration of sunitinib and its active metabolite is 50–87.5 ng/mL for the intermittent dosing schedule, ~10–21% of patients experience higher exposures (>87.5 ng/mL), correlated with an increased risk for toxicity. Previous research identified single nucleotide variants (SNVs) in genes from the sunitinib pharmacokinetic pathway to be associated with efficacy and toxicity. However, significant interindividual variability in exposure remains unexplained. Our aim was to identify genetic variants associated with supratherapeutic exposure of sunitinib.This was a genome‐wide association study. Cases were identified during routine therapeutic drug monitoring and consisted of patients with dose‐normalized sunitinib plasma concentrations >87.5 ng/mL (intermittent dosing) or >75 ng/mL (continuous dosing). Controls were sampled from the historical cohort EuroTARGET who tolerated the standard dose of 50 mg in an intermittent schedule. SNVs were tested for an association with sunitinib exposure. A P‐value ≤5 × 10−8 was considered significant and a P‐value between 5 × 10−8 and 5 × 10−6 was considered suggestive.Sixty‐nine cases and 345 controls were included for association analysis. One SNV (rs6923761), located on the gene glucagon‐like peptide 1 receptor, was significantly associated with increased sunitinib exposure (P = 7.86 × 10−19). Twelve SNVs were suggestive for an association with sunitinib exposure (P ≤ 5 × 10−6).While rs6923671 is associated with high sunitinib exposure, the underlying mechanism is not yet clarified and warrants further investigation. We could not confirm the earlier found associations between SNVs in candidate genes involved in the pharmacokinetic pathway of sunitinib and its efficacy and toxicity. [ABSTRACT FROM AUTHOR]

Folate-mediated one-carbon metabolism (FOCM) plays an important role in colorectal carcinogenesis. Previous studies have assessed the role of folate-mediated one-carbon metabolism (FOCM)-related gene-diet interaction in the aetiology of colorectal cancer (CRC), however, the results remained inconclusive. Thus, this study aimed to investigate dietary factors and genetic variants related to FOCM, as well as potential nutrient-gene and nutrient-lifestyle interactions, on CRC risk. This observational study included 229 patients diagnosed with CRC and 229 age- and sex-matched subjects as controls from a population-based bowel cancer screening program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) for CRC risk. A Bonferroni-corrected threshold of α = 0.005 was considered significant, and P values less than 0.05 were considered to be suggestive of an association. After Bonferroni correction, a high dietary intake of betaine was associated with a decreased risk of CRC in the adjusted model (OR, 95% CI: 0.21, 0.10–0.40, P < 0.001). Two SNPs, rs1476413 and rs17824591, exhibited significant gene-diet interactions with total choline ad vitamin B12 intakes, respectively, in adjusted models (total choline, tertile 3 vs. 1, OR, 95% CI: 0.25, 0.11–0.66, Pinteraction = 0.012; vitamin B12, tertile 2 vs. tertile 1, OR, 95% CI: 2.48, 1.04-5.00, Pinteraction = 0.003). These findings suggest that betaine intake and interactions between some dietary factors and variants in MTHFR and MTHFD1 genes have an influence on CRC risk in the population studied. If these results are confirmed, specific nutritional intervention strategies could be designed. [ABSTRACT FROM AUTHOR]

Nonetheless the key roles of growth hormone (GH) and insulin growth factor-1 (IGF-1) genes in livestock growth traits (including body measurements), few studies deployed them in camels, unlike other livestock species (cattle, buffalo, sheep, and goat). So, this study was performed to investigate the genetic polymorphism of GH and IGF-1 markers, in Maghrabi camels by PCR-SSCP and DNA sequencing tools, with assessing the impacted live body measurements traits. In this study, 65 blood samples were collected from Maghrabi camel, and different body measurements were valued. Different genotypes of GH and IGF-1 genes were determined, via SSCP-PCR and sequencing tools. The results pointed out one genotype for the IGF-I gene, and three genotypes for the GH gene, with 23.21, 42.85, and 33.95 frequencies, of AA, AB, and BB genotypes, respectively. The sequence analysis showed specific single nucleotide polymorphisms (SNPs), for both A and B alleles. Those SNPs triggered alteration in some of the amino acids. Moreover, individuals of the BB genotype recorded the highest value in body weight, Neck length, Height at lumbar area, Anterior limb length, Neck circumference, and increased Body length associated with the AA genotype. Nevertheless, there were no significant differences, between the three genotypes, for the other body measurements. This study found that Maghrabi camels possess three genotypes of the GH gene and one genotype of the IGFI gene, and the BB genotype of the GH gene was associated with high performance of growth traits. Therefore, it is useful to use camel individuals, with the BB genotype of the GH gene, in camelid breeding programs, to improve live body measurement traits. [ABSTRACT FROM AUTHOR]

This open-labeled and comparative study aimed to test the efficacy and safety of a fermented rice extract-based substance containing yeast-fermented powder having aldehyde dehydrogenase (KisLip®, Pico Entech, Republic of Korea) in healthy male individuals. Healthy male subjects (n = 20) consumed 90 g of alcohol at their first visit. At the second visit, participants consumed 90 g of alcohol or alcohol with a low dose of KISLip® (2000 mg, KL-L) and then 90 g of alcohol or alcohol with a high dose of KISLip® (3000 mg, KL-H) at the third visit. The efficacy of KISLip® depends on the mutational status of important genes related to alcohol metabolism, including alcohol dehydrogenase (ADH1B), cytochrome P4502E1 (CYP2E1 (5B) and CYP2E1 (6)), and aldehyde dehydrogenase (ALDH2). KISLip® significantly reduced the highest level (Cmax) of alcohol and overall levels of acetaldehyde compared to the alcohol-only group in a dose-dependent manner. These significant effects of KISLip® on alcohol metabolism were observed independent of mutations in the four genes. In addition, hangover symptoms were significantly decreased in the KISLip® treated groups. During the study, the participants did not show any adverse events after KISLip® intake. This clinical study suggested that supplementation of KISLip® had beneficial effects on alcohol metabolism and might ameliorate the severity of hangovers without any adverse events. [ABSTRACT FROM AUTHOR]

• Exploring the mechanism of tremor induction during VPA metabolism using gene variants as an entry point. • Genotyping UGT1A6 may help guide therapeutic decisions. • UGT1A6 A541G genotype can be used as one of the predictors to have VPA associated tremors. Individual susceptibility to sodium valproate (VPA)-induced tremors may be due to genetic polymorphisms in the gene encoding the uridine diphosphate glucuronosyltransferase (UGT) enzyme, which affec the drug's clinical efficacy and cause toxic side effects. This study aimed to investigate the association between UGT1A6 polymorphisms and VPA-induced tremors in patients with epilepsy. In total, 128 patients with epilepsy were enrolled. Patients with epilepsy who received VPA were divided into tremor and non-tremor groups. Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the genotype of UGT1A6 polymorphisms. Carriers of the UGT1A6 A541G mutant genotype conferred a higher risk of tremor than wild-type carriers (odds ratio 2.128, P = 0.045). Logistic regression analysis showed that the A541G mutant genotype was a significant genetic risk factor for VPA-induced tremors. This suggests that individual susceptibility to VPA-induced tremors may result, at least partially, from genetic variation in UGT1A6 A541G. Patients with epilepsy carrying the UGT1A6 A541G mutant genotype may have VPA-induced tremors, and early detection of this genotype will help guide the clinical individualizsation of VPA treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore genetic variations associated with DNA repair mechanisms to enhance the management of both oral cancer (OC) and oral precancer (OPC). Methods: A cohort of 380 patients diagnosed with OC and OPC, comprising 220 males and 160 females, was analyzed. Participants were categorized based on their tobacco-chewing habits, with corresponding control groups established. Key genetic markers investigated for polymorphisms included OGG1, APE1, and XRCC1. Results: The XRCC1 Arg280H variant demonstrated significant associations with the susceptibility to both OC and OPC across various models. Further analyses, incorporating factors such as tobacco and alcohol consumption, unveiled a correlation between the XRCC1 Arg194Trp variant and an elevated risk of developing head and neck cancer. Stratified analyses also revealed an increased risk of OC or OPC based on the specific site of the cancer. Conclusion: The study underscores the importance of XRCC1 polymorphisms, particularly XRCC1 Arg280H and XRCC1 Arg194Trp, within the genetic framework of OC and OPC. Understanding these genetic associations provides valuable insights for the potential development of targeted interventions aimed at individuals predisposed to these conditions. [ABSTRACT FROM AUTHOR]

This paper discusses the abundance and morphogenetic parameters of the species Adonis villosa Ledeb., which is vulnerable in the Altai Republic (AR). Genetic differentiation has been identified in six A. villosa coenopopulations (CPs) using ISSR markers and the variability of its morphometric parameters has been determined in individuals from four CPs inhabiting the AR for the first time. It is established that the studied CPs are similar in variability of morphometric parameters, and the number of mature generative individuals in them has decreased 1.5–2.0 times over the period from 2017 to 2023. The genetic structure is examined using six primers: M 9, UBC 834, UBC 830, UBC 857, UBC 840, and UBC 811; UBC-857 turned out to be the most informative one. Four variants of the distribution of ISSR markers are identified in representatives of the six studied A. villosa CPs that feature a high (88–99%) similarity in the distribution of ISSR markers. Intrapopulation similarity between individuals of this species is also high (97%). Apparently, this is due to the small numbers of mature generative individuals (up to ten) in the studied CPs and their spatial isolation. In the Northern Altai region, A. villosa individuals feature a homogeneous genetic structure, which makes this species vulnerable and necessitates a special approach to its conservation. [ABSTRACT FROM AUTHOR]

There are conflicting reports regarding the association of angiotensin 1 converting enzyme (ACE) gene polymorphism with diabetic retinopathy (DR). We compared ACE gene insertion/deletion (I/D) polymorphism between patients with and without DR in a middle-aged Indian population. The secondary outcome measure was the comparison of ACE gene I/D polymorphism in different grades of DR severity.Institutional cross-sectional case-control study with middle-aged (45–64 years) type 2 diabetes patients from Eastern India with DR (DR group) and without DR (NODR group). Polymerase chain reaction (PCR) was used to determine the ACE gene I/D polymorphism through primers flanking the polymorphic region of 287 bp Alu repeat sequence in intron 16.Genotyping for the ACE gene I/D polymorphisms were done for 107 patients in each group. The presence of DR had no significant association with the prevalence of ACE I/D genotype compared to those without DR either in the recessive model (p=0.588) or in the dominant model (p=0.891). The allele contrast was also similar between DR and NODR (p=0.837) groups. The severity of retinopathy was associated with the ACE I/D genotype in the recessive model (p=0.043) but not in the dominant model (p=0.136). However, the severity of retinopathy was associated with allele contrast (p=0.016).The ACE gene polymorphism was not associated with diabetic retinopathy in middle-aged Indian patients with type 2 diabetes in our study. However, the severity of DR was associated with the ACE gene polymorphism in these patients. [ABSTRACT FROM AUTHOR]

The secreted phospholipase A2 (sPLA2) isoform, sPLA2-IIA, has been implicated in a variety of diseases and conditions, including bacteremia, cardiovascular disease, COVID-19, sepsis, adult respiratory distress syndrome, and certain cancers. Given its significant role in these conditions, understanding the regulatory mechanisms impacting its levels is crucial. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs), including rs11573156, that are associated with circulating levels of sPLA2-IIA. The work in the manuscript leveraged 4 publicly available datasets to investigate the mechanism by which rs11573156 influences sPLA2-IIA levels via bioinformatics and modeling analysis. Through genotype-tissue expression (GTEx), 234 expression quantitative trait loci (eQTLs) were identified for the gene that encodes for sPLA2-IIA, PLA2G2A. SNP2TFBS was used to ascertain the binding affinities between transcription factors (TFs) to both the reference and alternative alleles of identified eQTL SNPs. Subsequently, candidate TF-SNP interactions were cross-referenced with the ChIP-seq results in matched tissues from ENCODE. SP1-rs11573156 emerged as the significant TF-SNP pair in the liver. Further analysis revealed that the upregulation of PLA2G2A transcript levels through the rs11573156 variant was likely affected by tissue SP1 protein levels. Using an ordinary differential equation based on Michaelis-Menten kinetic assumptions, we modeled the dependence of PLA2G2A transcription on SP1 protein levels, incorporating the SNP influence. Collectively, our analysis strongly suggests that the difference in the binding dynamics of SP1 to different rs11573156 alleles may underlie the allele-specific PLA2G2A expression in different tissues, a mechanistic model that awaits future direct experimental validation. This mechanism likely contributes to the variation in circulating sPLA2-IIA protein levels in the human population, with implications for a wide range of human diseases. [ABSTRACT FROM AUTHOR]

Background: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. Methods: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. Results: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. Conclusions: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups. [ABSTRACT FROM AUTHOR]

Background and aims: Anorexia nervosa (AN) is a complex neuropsychiatric disorder. This systematic review synthesizes evidence from diverse studies to assess and investigate the association between gene polymorphisms and psychological and neurobiological factors in patients with AN. Methods: A systematic search across PubMed, PsycINFO, Scopus, and Web of Science databases, along with manual searching, was conducted. The review protocol was approved by PROSPERO (CRD42023452548). Out of 1,250 articles, 11 met the inclusion criteria. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale (NOS) tool. The systematic review followed the PRISMA guidelines. Results: The serotoninergic system, particularly the 5-HTTLPR polymorphism, is consistently linked to altered connectivity in the ventral attention network, impaired inhibitory control, and increased susceptibility to AN. The 5-HTTLPR polymorphism affects reward processing, motivation, reasoning, working memory, inhibition, and outcome prediction in patients with AN. The dopaminergic system, involving genes like COMT, DRD2, DRD3, and DAT1, regulates reward, motivation, and decision-making. Genetic variations in these dopaminergic genes are associated with psychological manifestations and clinical severity in patients with AN. Across populations, the Val66Met polymorphism in the BDNF gene influences personality traits, eating behaviors, and emotional responses. Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN. Conclusion: There was an association linking multiple genes to the susceptibly and/or severity of AN. This genetic factor contributes to the complexity of AN and leads to higher diversity of its clinical presentation. Therefore, conducting more extensive research to elucidate the underlying mechanisms of anorexia nervosa pathology is imperative for advancing our understanding and potentially developing targeted therapeutic interventions for the disorder. [ABSTRACT FROM AUTHOR]

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of the most consistent pathophysiological findings in depressive disorders. Cortisol signaling is affected by proteins that mediate its cellular responses or alters its availability to mineralocorticoid and glucocorticoid receptors. In our study, we evaluated candidate genes that may influence the risk for depression and suicide due to its involvement in cortisol signaling. The aim of the study was to assess whether the genotypes of these genes are associated with the risk for depression, severity of depressive symptoms, suicidal ideation, and suicide attempts. And whether there is interaction between genes and early-life stress. In this study, 100 healthy controls and 140 individuals with depression were included. The subjects were clinically assessed using the 21-item GRID-Hamilton questionnaires (GRID-HAMD-21), Beck Scale for Suicidal Ideation (BSI), and the Childhood Trauma Questionnaire (CTQ). A robust multifactorial dimensionality reduction analysis was used to characterize the interactions between the genes HSD11B1 , NR3C1, NR3C2 , and MDR1 and early-life stress. It was found a significant association of the heterozygous genotype of the MDR1 gene rs1128503 polymorphism with reduced risk of at least one suicide attempt (OR: 0.08, p = 0.003*) and a reduction in the number of suicide attempts (β = −0.79, p = 0.006*). Furthermore, it was found that the MDR1 rs1228503 and NR3C2 rs2070951 genes interact with early-life stress resulting in a strong association with depression (p = 0.001). Our findings suggest that polymorphisms in the MDR1 and NR3C2 genes and their interaction with childhood trauma may be important biomarkers for depression and suicidal behaviors. [ABSTRACT FROM AUTHOR]

Purpose: Genetic factors are important in terms of athletic performance. Recent studies to determine the relationship between the genes that lead to physiological responses have attracted attention. In this respect, this meta-analysis study was designed to examine the relationship between genetic polymorphism (BDKRB2 rs5810761, GNB3 rs5443, HIF1A rs11549565, MCT1 rs1049434, NOS3 rs2070744) and endurance athlete's status. Methods: The search included studies published from 2009 to 2022. To determine the relevant studies, Pubmed, Web of Science databases were systematically scanned. Only case-control studies were included in the meta-analysis. To determine the relevant studies, Pubmed, Web of Science databases were systematically scanned, and a total of 31 studies met the criteria for inclusion in the meta-analysis. Relevant data from the included studies were collected and analyzed using a random effects or fixed effects model. The effect size was calculated as the odds ratio or a risk ratio the corresponding 95% confidence intervals. Results: According to the results of the analysis, BDKRB2 rs5810761 + 9 allele, and NOS3 rs2070744 T allele were significantly more prevalent in endurance athletes (p < 0.05). Genotype distributions of BDKRB2 rs5810761, MCT1 rs1049434, and NOS3 rs2070744 showed significant differences in the dominant model (p < 0.05). However, no significant association was found between endurance athlete status and GNB3 rs5443 and HIF1A rs11549465 polymorphisms. Conclusion: These results show that some gene polymorphisms play an important role in endurance athlete status and suggest that having a specific genetic basis may also confer a physiological advantage for performance. [ABSTRACT FROM AUTHOR]

Objective To analyze the distribution bio-relationship of loci related antihypertensive drug efficacy in patients with essential hypertension (EH) in Guiyang region to support the development of clinical guidance for in- dividualized medication of hypertension patients in this region. Methods A total of 406 EH patients who visited the Cardiology Department of Guiyang Hospital from December 2020 to December 2021 were collected as the study sub- jects and ligase sequencing method was applied to detect 7 gene loci of antihypertensive drugs. The distribution of gene loci in EH patients of different genders and from different geographic regions was evaluated. Results The mu- tation frequencies of the seven genes, CYP2D6 10(c. 100 C>T), CYP2C93(c. 1075 A>C), ADRB1 (c. 1165 G>C), AGTR1 (c. 1166 A>C), ACE (I/D), NPPA (T2238C) and CYP3A5 3 (A6986G) were 47.29%, 5.91%, 73.15%, 6.65%, 34.24%, 0.49%, and 69. 70% respectively; There was no significant difference in distribution frequency of hypertension drug related gene polymorphisms among different genders. Conclusions The distribution frequency of alleles in 7 antihypertensive drug efficacy related loci is not related to gender of patients. EH patients in Guiyang region are more sensitive to B-blockers and calcium antagonists, but less sensitive to other types of antihypertensive drugs. Therefore, the dose administered should be adjusted appropriately when using B-blockers and calcium antagonists. [ABSTRACT FROM AUTHOR]

Rheumatic heart disease (RHD) caused by group A streptococcus infection is one of the most important reasons of cardiovascular morbidity and mortality in low- and middle-income countries. Aberrant host immune response modulated by polymorphisms in inflammatory response genes plays an important role in RHD pathogenesis. This study aimed to determine risk-associated polymorphic variants in inflammatory response genes in Caucasian RHD patients. A total of 251 Caucasian RHD patients and 300 healthy donors were recruited for this study, and 27 polymorphic sites in 12 genes (TLR1, TLR2, TLR4, TLR6, IL1B, IL6R, IL6, IL10, IL12RB1, IL12B, TNF and CRP) were analyzed using allele-specific PCR. It was demonstrated that the polymorphic variants rs1800871 and rs1800872 in the IL10 gene, rs 1130864, rs3093077 and rs1205 in the CRP gene, rs375947 in the IL12RB1 gene, rs 5743551 and rs5743611 in the TLR1 gene, and rs3775073 in the TLR6 gene can modify RHD risk in a gender- and age-dependent manner. The obtained results can be used to determine the personalized risk of RHD in healthy donors during medical examination or screening, as well as to develop appropriate early prevention strategies targeting RHD in the risk groups. [ABSTRACT FROM AUTHOR]

Objective To obtain the distribution of allele frequency and population genetic data of 23 autosomal STR loci contained in the MicroreaderTM 23HS Plex ID System kit in the Han population of northern China, and explore its application value in forensic medicine. Methods The MicroreaderTM 23HS Plex ID System kit was used to detect the DNA of 548 unrelated samples which from the Han population in northern China. Then, the allele frequencies, heterozygosity (H) in the samples, polymorphism information content (PIC), power of discrimination (DP), and probability of paternity exclusion (PE) were calculated and Hardy-Weinberg equilibrium was tested on each locus based on the genotyping data of 548 samples we collected. The cumulative individual identification ability (CDP) and cumulative non-paternity exclusion rate (CPE) of the MicroreaderTM 23HS Plex ID System were also calculated. Results A total of 260 alleles were detected in 548 unrelated samples from 23 STR loci which conformed to Hardy-Weinberg equilibrium. And the alleles frequencies ranged from 0.000 9 to 0.590 2, H ranged from 0.611 to 0.885, PIC ranged from 0.577 to 0.864, DP ranged from 0.815 to 0.973 (mean DP was 0.922) and PE ranged from 0.089 to 0.406. At the same time, the CDP of MicroreaderTM 23HS Plex ID System was 1- 3.663×10-27 and CPE was 1-2.668×10-16. Conclusion The 23 loci of MicroreaderTM 23HS Plex ID System have a good polymorphism in the north Chinese Han population, and have high application value in population genetics research, forensic personal identification, paternity testing and complex kinship identification. [ABSTRACT FROM AUTHOR]

Objective: Gene polymorphisms CDKAL1 (rs7754840) have been related to type 2 diabetes mellitus, which may partially define the common genetic background with gestational diabetes mellitus (GDM). The aim of this study is to investigate the association between CDKAL1 polymorphism and susceptibility to GDM. Methods: In this study and meta-analysis, we conducted a systematic search in electronic databases such as PubMed, Web of Science, Scopus, Cochrane, EMBASE, and Google scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association between CDKAL1 (rs7754840) polymorphisms and susceptibility to GDM in four genetic models. Statistical analysis was performed by Comprehensive Meta-Analysis (CMA) v3.7z software. Results: A total of 13,307 participants from 11 original study were included in this study. We identified a significant relationship between the CDKAL1 (rs7754840) gene polymorphism and GDM in the study population through allelic models (C vs. G: OR = 1.29, 95% CI = 1.16–1.44, p = 0.00), homozygous genetic models (CC vs. GC: OR = 1.50, 95% CI = 1.28–1.75, p = 0.00), recessive models (CC vs. GG + GC: OR = 0.67, 95% CI = 0.57–0.79, p = 0.00), and dominant genetic models (CC + GC vs. GG: OR = 1.35, 95% CI = 1.17–1.56, p = 0.00). On the contrary, there is no significant association between the CDKAL1 gene polymorphism and susceptibility to GDM in heterozygous models (GC vs. GG: OR = 1.01, 95% CI = 0.92–1.12, p = 0.82). Conclusion: The results provided evidence that CDKAL1 (rs7754840) gene polymorphism is associated with the susceptibility of GDM in women. [ABSTRACT FROM AUTHOR]

Benzene is used worldwide as a major raw material in a number of industrial processes and also a potent airborne pollutant emitted from traffic exhaust fume. The present systematic review aimed to identify potential associations between genetic polymorphisms and occupational benzene-induced genotoxicity. For this purpose, a total of 22 selected studies were carefully analysed. Our results revealed a positive relation between gene polymorphism and genotoxicity in individuals exposed to benzene, since 17 studies (out of 22) observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes influencing, therefore, individuals' susceptibility to genomic damage induced by benzene. In other words, individuals with some genotypes may show increase or decrease DNA damage and/or higher or lower DNA-repair potential. As for the quality assessment, 17 studies (out of 22) were categorized as Strong or Moderate and, therefore, we consider our findings to be trustworthy. Taken together, such findings are consistent with the notion that benzene induces genotoxicity in mammalian cells being strongly dependent on the genetic polymorphism. Certainly, such findings are important for clarifying the role of biomarkers related to genotoxicity in human biomonitoring studies. [ABSTRACT FROM AUTHOR]

Introduction: Vascular dementia (VaD), a neurocognitive impairment directly related to vascular injury, is the second most common cause of age-related dementia. Although numerous studies have investigated candidate genetic polymorphisms associated with VaD in Asia, the genetics of VaD remains unclear. Methods: This review provides an updated meta-analysis of genetic polymorphisms associated with VaD in Asians, using the PRISMA guidelines. Published literature up to May 2021 was extracted from the PubMed, Scopus, Ovid, and EBSCOhost databases. Meta-analysis was conducted using the Open Meta analyst, Review Manager, and MedCalc® Statistical Software. Trial sequential analysis (TSA) was performed using TSA viewer software. Results: A total of 46 eligible studies, comprising 23 genes and 35 single nucleotide polymorphisms, were retrieved. The meta-analysis was conducted on the following genetic polymorphisms, APOE ε2/3/4, MTHFR rs1801131, ACE rs4340 (I/D) gene polymorphism, and a PSEN1 intron 8 variant. The pooled odds ratio (ORs) revealed a significant increase in the risk of VaD in the apolipoprotein E (APOE) ε4 allelic model (OR, 1.79, p < 0.001), and the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism T allele in the allelic model (OR, 1.23, p = 0.013). Conclusion: Our findings provide evidence that genetic polymorphisms of the APOE ε4 allele and MTHFR rs1801133 T allele increase the risk of developing VaD in Asians. However, future large-scale investigations examining particularly on South-Eastern and West-Asian populations are highly recommended. [ABSTRACT FROM AUTHOR]

Melanin-based color polymorphism is predicted to evolve and maintain through differential fitness of morphs in different environments, and several empirical studies indicate that life history strategies, physiology, and behavior vary among color morphs. Sex allocation theory predicts that parents should adjust their sex allocation based on differential costs of raising sons and daughters, and therefore, color morphs are expected to modify their brood sex ratio decisions. In color polymorphic tawny owls (Strix aluco), the pheomelanistic brown morph is associated with higher energy requirements, faster growth, and higher parental effort than the gray morph. As hypothesized, we find that brown tawny owl mothers produced more daughters in early broods and more males in late broods, whereas gray mothers did the opposite. At fledging, daughters of early broods and of brown mothers were heavier than those of late broods or gray mothers. Hence, larger and more costly daughters appeared to benefit more than males from being born to brown mothers early in the season. Brown mothers breeding later in the season produced more cheap sons, while gray mothers face fewer challenges under limited resources and favor daughters. These findings suggest that environmental conditions influence brood sex allocation strategies of genetically determined color morphs differently. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a systematic autoimmune disorder characterized by the production of autoantibodies against nuclear antigens and inflammation initiation. We aimed to examine the correlation between IL-18, IL-37, and PD-1, and the potential link between polymorphisms in the PD-1 gene located in intron-4 and the susceptibility to SLE. MATERIALS AND METHODS: This cross-sectional study included 43 SLE and 53 healthy individuals. Blood samples were obtained and underwent biochemical examination. The polymorphisms were screened by amplifying the intron-4 of the PD-1 gene using particular primers and then verified through sequencing. RESULTS: Our findings demonstrated statistically significant positive correlations between IL-18, IL-37, and PD-1, while the AUC of the ROC curve is 0.985, 0.968, and 0.940, and cut-off concentration is ≥132.87, ≥62.98, and ≥169.02, respectively. Moreover, two separate SNPs (rs6705653 and rs41386349) were discovered within intron-4 of the PD-1 gene. The genotype AA of the +7499 (G/A) SNP was significantly related with an increased risk of SLE (OR=3.11, 95%CI=1.52–5.94, p-value=0.031). Additionally, the A allele was identified as a risk allele (OR=1.59, 95%CI=1.09–2.31, p-value=0.043). Nevertheless, our study didn’t find any noteworthy connection between the allele and genotype of the +7209 (C/T) polymorphism region of the PD-1 gene frequencies and the susceptibility to SLE. CONCLUSION: IL-18, IL-37, and PD-1 may play significant roles in SLE immune responses and processes. Furthermore, the sequencing examination of intron-4 within the PD-1 gene demonstrated a noteworthy correlation between the A allele and the AA genotypes of PD-1 +7499 (G/A) SNP presence with the increased SLE susceptibility. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion The phenotypic consequences of the p.Arg577Ter variant in the α‐actinin‐3 (ACTN3) gene are suggestive of a trade‐off between performance traits for speed and endurance sports. Although there is a consistent association of the c.1729C allele (aka R allele) with strength/power traits, there is still a debate on whether the null allele (c.1729T allele; aka X allele) influences endurance performance. The present study aimed to test the association of the ACTN3 p.Arg577Ter variant with long‐distance endurance athlete status, using previously published data with the Brazilian population.Genotypic data from 203 long‐distance athletes and 1724 controls were analysed in a case–control approach.The frequency of the X allele was significantly higher in long‐distance athletes than in the control group (51.5% vs. 41.4%; p = 0.000095). The R/X and X/X genotypes were overrepresented in the athlete group. Individuals with the R/X genotype instead of the R/R genotype had a 1.6 increase in the odds of being a long‐distance athlete (p = 0.012), whereas individuals with the X/X genotype instead of the R/R genotype had a 2.2 increase in the odds of being a long‐distance athlete (p = 0.00017).The X allele, mainly the X/X genotype, was associated with long‐distance athlete status in Brazilians. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response. Methods: To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta‐analysis using the Review Manager software. Results: Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI). Conclusion: Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer. [ABSTRACT FROM AUTHOR]

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Aim: This paper determines the polymorphism distribution of the VDR BsmI gene in 350 patients and provides medication recommendations for osteoporosis based on detection results. Materials & methods: Chi-square tests compared genotype and allele frequencies with other populations. Results: Genotype frequencies were 91.66 bb, 8.72 Bb and 0.21% BB, with allelic frequencies of 95.43 b and 4.57% B, adhering to Hardy–Weinberg equilibrium. These findings suggest that VDR gene polymorphisms, particularly at the BsmIlocus, play an essential role in bone health and osteoporosis treatment. Genotype-based drug selection reduced adverse reactions from 14 to two cases. Conclusion: These findings improve clinical treatment efficacy and guide rational drug use for osteoporosis patients. Article highlights Objective To determine the polymorphism distribution of the vitamin D receptor (VDR) BsmI locus gene in osteoporosis patients and provide medication recommendations. Methods Genetic testing of 350 patients for VDR BsmI gene polymorphisms, comparison of genotype and allele frequencies, and assessment of the impact on drug selection. Significance Understanding the role of VDR gene polymorphisms in bone health and treatment response, and the potential for genotype-based drug selection. Results Genotype distribution: The study identified three genotypes at the BsmI locus: bb (91.66%), Bb (8.72%) and BB (0.21%), with allele frequencies of 95.43% for b and 4.57% for B. This distribution aligns with the Hardy–Weinberg equilibrium, indicating a representative sample. Comparison with other populations: The VDR gene allele frequencies in the Guangdong Han population significantly differ from those in South Asia, America, Europe and Africa but are similar to other East Asian populations. Impact on bone mineral density: There was no significant difference in bone mineral density T-scores before and after treatment across the different VDR genotypes, but patients with the b allele showed better responses to osteoporosis treatments, particularly with bisphosphonates. Adverse drug reactions (ADRs): before genetic testing, there were 14 ADRs, which reduced to only two cases post implementation, indicating improved treatment outcomes and reduced side effects through genotype-based drug selection. Conclusions The study supports the importance of genetic testing in guiding osteoporosis treatment as VDR gene polymorphisms, particularly at the BsmI locus, significantly influence treatment efficacy and the occurrence of ADRs. Genotype-based drug selection can improve clinical outcomes and minimize side effects. The findings suggest the need for further research on the distribution and impact of VDR BsmI locus polymorphism in different Chinese populations. Large-scale, multicenter studies are recommended to validate these results and enhance the precision of genotype-based drug recommendations. Integrating pharmacogenomics into clinical practice promises to improve the effectiveness of osteoporosis treatments, minimize adverse reactions, and advance personalized medicine, ultimately enhancing patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

The genetic diversity of killer cell immunoglobulin‐like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA‐A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case‐control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA‐A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA‐A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection. [ABSTRACT FROM AUTHOR]

(1) Background: This study was aimed to identify universal genetic markers of multidrug resistance (MDR) in Mycobacterium tuberculosis (Mtb) and establish statistical associations among identified mutations to enhance understanding of MDR in Mtb and inform diagnostic and treatment development. (2) Methods: GWAS analysis and the statistical evaluation of identified polymorphic sites within protein-coding genes of Mtb were performed. Statistical associations between specific mutations and antibiotic resistance were established using attributable risk statistics. (3) Results: Sixty-four polymorphic sites were identified as universal markers of drug resistance, with forty-seven in PE/PPE regions and seventeen in functional genes. Mutations in genes such as cyp123, fadE36, gidB, and ethA showed significant associations with resistance to various antibiotics. Notably, mutations in cyp123 at codon position 279 were linked to resistance to ten antibiotics. The study highlighted the role of PE/PPE and PE_PGRS genes in Mtb's evolution towards a 'mutator phenotype'. The pathways of acquisition of mutations forming the epistatic landscape of MDR were discussed. (4) Conclusions: This research identifies marker mutations across the Mtb genome associated with MDR. The findings provide new insights into the molecular basis of MDR acquisition in Mtb, aiding in the development of more effective diagnostics and treatments targeting these mutations to combat MDR tuberculosis. [ABSTRACT FROM AUTHOR]

Abstract Background Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. Methods Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. Results The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017–5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073–5.396, P = 0.033). Conclusions NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS.

Objective To analyze the distribution bio-relationship of loci related antihypertensive drug efficacy in patients with essential hypertension (EH) in Guiyang region to support the development of clinical guidance for individualized medication of hypertension patients in this region. Methods A total of 406 EH patients who visited the Cardiology Department of Guiyang Hospital from December 2020 to December 2021 were collected as the study subjects and ligase sequencing method was applied to detect 7 gene loci of antihypertensive drugs. The distribution of gene loci in EH patients of different genders and from different geographic regions was evaluated. Results The mutation frequencies of the seven genes, CYP2D6*10(c.100 C＞T),CYP2C9*3(c.1075 A＞C),ADRB1(c.1165 G＞C),AGTR1(c.1166 A＞C),ACE(I/D),NPPA(T2238C) and CYP3A5*3(A6986G) were 47.29%, 5.91%, 73.15%, 6.65%, 34.24%, 0.49%, and 69.70% respectively; There was no significant difference in distribution frequency of hypertension drug related gene polymorphisms among different genders. Conclusions The distribution frequency of alleles in 7 antihypertensive drug efficacy related loci is not related to gender of patients.EH patients in Guiyang region are more sensitive to β-blockers and calcium antagonists, but less sensitive to other types of antihypertensive drugs. Therefore, the dose administered should be adjusted appropriately when using β-blockers and calcium antagonists.

Asthma is one of the most common chronic diseases in all age groups. Asthma has heterogeneous phenotypes with different etiologies. Many parameters are used to classify asthma, for example, the severity and level of flow control. The asthma phenotype is dependent on the state of the immune system, and innate immunity plays an important role in the susceptibility and pathophysiology of asthma. The complement system (CS) consists of a complex of protective proteolytic enzymes (including lectins). Ficolin-2 (L-ficolin) is one of the main opsonizing molecules of respiratory secretions and a protein of the lectin pathway of CS activation. Polymorphisms in the L-ficolin gene affect the level of expression which may be associated with a higher susceptibility to infections and viruses, as well as a predisposition to asthma.Aim: To study the distribution of polymorphisms rs17549193 and rs7851696 of the L-ficolin (FCN2) gene in children with asthma of varying severity.Russian children from the Children’s Allergy Center (Krasnoyarsk, Russia), aged from 8 to 18 years, were studied. Children with asthma were divided into groups depending on the severity of the disease in accordance with GINA-2023: mild (n = 146) and severe (n = 254). The comparison group included children of comparable age and gender without asthma, allergies or infections. DNA extraction from blood was performed using the sorbent method. Genotyping of polymorphisms rs17549193 and rs7851696 FCN2 was performed by real-time polymerase chain reaction.The results obtained provide distribution of the polymorphic variants FCN2 gene in the population of healthy Russian children and in children with a socially and economically important disease, namely asthma. The distribution of rs17549193 and rs7851696 FCN2 corresponds to the global Caucasoid populations. There were no statistically significant differences between asthma patients with varying degrees of severity of the disease and healthy ones in the studied sample.The results indicate an expansion of the sample and range of studied polymorphic genes of proteins of the lectin pathway of CS activation due to their importance for the prevention of severe forms of diseases, as well as their significance in the functioning of the immune system.

Abstract Background There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. Methods HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. Results Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. Conclusions Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

The aim was to evaluate near-infrared spectroscopy (NIRS) potential to discriminate among β-casein (CN), κ-CN and β-lactoglobulin (LG) genotypes to be used as an authentication method. A total of 168 milk samples with known genetic information for β-CN, κ-CN and β-LG were collected at the same farm and paired with the NIRS spectrum. Spectra were evaluated with an unsupervised method (principal component analysis, PCA) and a supervised method (partial least squares-discriminant analysis, PLS-DA). For the PLS-DA, data were split into a train (75%) and a test set (25%), and the variable in projection >1 criterion was applied to select informative wavelengths. Results obtained confirmed that milk quality was similar among genetic variants. For the PCA, the observed variance explained by the first two principal components was 94%, but samples were not clustered by their genotypes of β-CN (i.e. A1A2, A2A2), κ-CN (i.e. AA, AB, AE, BB, BE) and β-LG (i.e. AA, AB, BB). The best accuracy for the PLS-DA models was reached by β-CN (train and test set, 64%), followed by β-LG (train set, 56%; test set, 52%) and κ-CN (train set, 41%; test set, 36%). In conclusion, the PCA on milk spectra was not able to cluster β-CN, κ-CN and β-LG genotypes, but the PLS-DA models revealed promising results for β-CN and β-LG. It could be interesting to increase the number of samples to equilibrate genetic variants and to apply a sampling selection method before discarding the applicability of NIRS as an authentication method.

Background: Fibroblast growth factors (FGFs) play a key role in embryo implantation and support endometrial trophoblastic interaction. Aim: The aim of the study was to evaluate the association between FGF-1 (rs34011) gene variety and its serum concentration with repeated implantation failure (RIF). Setting and Design: The design of the study was a cross-sectional study. Materials and Methods: Four hundred infertile women with a history of RIF and 400 healthy women undergoing the first in vitro fertilisation-embryo transfer attempt with successful delivery (controls) were enrolled in the study. Genomic DNA was extracted from peripheral blood leucocytes and genotyped by Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction. Serum FGF-1 concentration was evaluated with enzyme-linked immunosorbent assay. Statistical Analysis Used: The ANOVA test was used to analyse the difference between the means of the groups. Results: In RIF group, the genotype frequencies of the GG, GA and AA were 59%, 33.5% and 7.5%, respectively, whereas in controls were 72.5%, 24% and 3.5%, respectively. The G and A allele frequencies in the RIF group were 75.75% and 24.25%, while in controls were 84.5% and 15.5%, respectively (P < 0.0001). We have also shown that serum FGF-1 concentration in RIF and control groups was 17 ± 3.55 and 23.62 ± 4.91 pg/mL, respectively (P = 0.008). We have also shown that AA genotype is significantly associated with decreased serum FGF-1 concentration in RIF (AA, GA and GG serum levels were 9.55 ± 2.65, 14 ± 3.35 and 22.55 ± 7.26 pg/mL, and in controls were 12.22 ± 2.27, 18.44 ± 5.98 and 26.66 ± 8.29 pg/mL, respectively). Conclusion: The current study suggests that a significant association between FGF-1 (rs34011) promoter polymorphism and its serum concentration with RIF. The study also suggests that AA genotype is linked to lower FGF-1 serum levels and may play a risk factor for RIF.

The aim of this study was to investigate the genetic structure of the experimental group of largemouth bass reared in the ponds of Polissia of Ukraine using ISSR markers. To accomplish these tasks, ISSR genotyping of the genetic structure of largemouth bass was performed using four fragments of trinucleotide loci. The genetic structure of the experimental group of largemouth bass of the pond fsh farm "Nyvka" was characterised using 4 primers B – (GAG)6C; C – (AGC)6G; D – (ACC)6G and E – (AGC)6C. Fins fragments were used for the study. In the course of the work, the optimal conditions for ISSR-PCR analysis were selected. The study revealed a number of factors that affect the efciency of these markers: DNA concentration, number of amplifcation cycles. For 4 markers, 80 alleles with a molecular weight of 160–1320 bp were identifed. The ranges of amplicons for the selected markers were determined: marker B – from 150 to 1186 bp; marker C – from 640 to 200 bp; D – from 1320 to 225 bp; and E – within 630–160 bp. The most polymorphic marker is marker B – 26 alleles, the least polymorphic marker is marker E – 15 alleles. In the studied experimental group of largemouth bass, the effective number of alleles varied from 10.2 for marker E to 12.2 for marker C, D. The indicators of genetic variability were determined by calculating allelic frequencies, the maximum level of available heterozygosity is 0.918 for marker C, D, and the lowest for marker E is up to 0.902. A method has been proposed that makes it possible to analyse the genetic structure of the experimental group of largemouth bass using these primers and to implement genetic information at different stages of the selection process.

Venous thromboembolism (VTE) is a challenging clinical obstacle in oncological settings, marked by elevated incidence rates and resulting morbidity and mortality. In the context of cancer-associated thrombosis (CAT), endothelial dysfunction (ED) plays a crucial role in promoting a pro-thrombotic environment as endothelial cells lose their ability to regulate blood flow and coagulation. Moreover, emerging research suggests that this disorder may not only contribute to CAT but also impact tumorigenesis itself. Indeed, a dysfunctional endothelium may promote resistance to therapy and favour tumour progression and dissemination. While extensive research has elucidated the multifaceted mechanisms of ED pathogenesis, the genetic component remains a focal point of investigation. This comprehensive narrative review thus delves into the genetic landscape of ED and its potential ramifications on cancer progression. A thorough examination of genetic variants, specifically polymorphisms, within key genes involved in ED pathogenesis, namely eNOS, EDN1, ACE, AGT, F2, SELP, SELE, VWF, ICAM1, and VCAM1, was conducted. Overall, these polymorphisms seem to play a context-dependent role, exerting both oncogenic and tumour suppressor effects depending on the tumour and other environmental factors. In-depth studies are needed to uncover the mechanisms connecting these DNA variations to the pathogenesis of malignant diseases.

Desi Reski Fajar,1,2 Tina Rostinawati,1 Laniyati Hamijoyo,3,4 Edhyana Sahiratmadja,4,5 Riezki Amalia,6,7 Melisa Intan Barliana1,7 1Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 2Institut of Pelamonia Health Sciences, Makassar, Indonesia; 3Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Bandung, Indonesia; 4Immunology Study Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; 5Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, Indonesia; 6Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Jatinangor, Indonesia; 7Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jatinangor, IndonesiaCorrespondence: Melisa Intan Barliana, Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Ir. Soekarno KM 21, Jatinangor, 45363, Indonesia, Tel +6281214451177, Email melisa.barliana@unpad.ac.idBackground: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous clinical manifestations. Organ involvement can aggravate patients with SLE and cause comorbidities such as atherosclerosis. Recently, the TNFSF13B gene has been found to be linked with SLE events. This study aimed to analyze the association between single nucleotide polymorphisms of the TNFSF13B rs9514828 with incidence of atherosclerosis and therapeutic outcomes in patients with SLE.Patients and Methods: This case-control study included 84 SLE patients, of whom 21 patients with SLE with atherosclerosis and 63 patients with SLE without atherosclerosis. Using enzyme-linked immunosorbent assay method, interleukin-6 and interferon gamma levels were quantified. The TNFSF13B gene polymorphism was evaluated using polymerase chain reaction followed by sequencing. The lupus low disease activity state (LLDAS) criteria were used to measure the therapeutic outcomes. Statistical analysis was conducted using binary logistic regression.Results: The genetic variations of TNFSF13B rs9514828 were CC = 35, CT = 41, and TT = 8. There was an association between TNFSF13B rs9514828 C>T polymorphism in patients with SLE with and without atherosclerosis (p = 0.03; odds ratio (OR) 4.72, 95% confidence interval [CI] 1.22– 18.37). Furthermore, the TNFSF13B rs9514828 C>T polymorphism had association with the therapeutic outcomes of patients with SLE who manifested with LLDAS (p = 0.00; OR 7.58, 95% CI 2.61– 21.99).Conclusion: The association of TNFSF13B rs9514828 C>T polymorphism and incidence of atherosclerosis as well as the therapeutic outcomes in patients with SLE indicate the potential utility of the gene variation as screening tool to employ personalized medicine to undertake preventive measures in order to prevent atherosclerosis and to predict a poor prognosis in SLE patient.Keywords: systemic lupus erythematosus, atherosclerosis, genetic polymorphism, TNFSF13B, LLDAS

Background and Aim: Age-related hearing loss (ARHL) is thought to be linked to an increase in oxidative stress in the cochlea. Glutathione S-transferase enzymes (GSTs) play a crucial role as antioxidant enzymes in the cochlea. The aim of this study was to evaluate the association between the rs4891 polymorphism in the GSTP1 gene and the risk of ARHL. Methods: This case-control study involved the examination of 90 individuals with ARHL and 100 healthy individuals. Genomic DNA was extracted from blood samples, and the PCR-RFLP technique was used to determine the genotypes of the GSTP1-rs4891 polymorphism. Logistic regression analysis was conducted to investigate the relationship between genotypes and the risk of ARHL. The odds ratio and 95% confidence interval were calculated. Results: The results showed that the TC and CC genotypes were not found to be associated with the risk of ARHL. However, analysis using the dominant model revealed that C allele carriers were at a higher risk of ARHL (P=0.032, 95% CI=0.94-3.23, OR=1.882). Allelic analysis also indicated an association between the C allele and ARHL (P=0.019, 95% CI=1.09-2.65, OR=1.700). Moreover, the CT (P=0.0181, 95% CI=7.8927-1.2127, OR=3.0938) and CC (P=0.0029, 95% CI=64.6308-2.3695, OR=12.3750) mutant genotypes were associated with an increased risk of ARHL with increasing age. Conclusion: The findings suggest that the GSTP1-rs4891 polymorphism may serve as a molecular risk factor for ARHL, particularly in older individuals. However, further studies with larger sample sizes are warranted to validate these findings.

The corona virus disease-2019 (COVID-19) pandemic has affected most of the world with varying degrees of morbidity and mortality. The presence of genetic polymorphisms may be associated with the severity and outcome of COVID-19 infection. This work aimed to evaluate the genetic polymorphisms of interleukin (IL-6) and IL-10 genes with the outcome of COVID-19 infection. This cross-sectional study was conducted on 354 patients who were classified into moderate and severe cases (including alive and deceased cases). All individuals were genotyped for one SNP for IL-6 (rs1800795) and one SNP for IL10 (rs1800896) using allelic discrimination real-time PCR technique. In this study, 198 cases were moderate, and 156 cases were severe. The risk of allele carriage of the minor allele of IL-6 rs1800795 (C) was significantly higher among the severe group when compared with that of the moderate group (p < 0.0001), while there was a mild significant difference of same allele carriage among alive cases when compared to that of deceased one (p < 0.04). Furthermore, the risk of the C allele of IL-10 rs1800896 was significantly increased in severe cases when compared with the moderate group (p < 0.0001), while there was no significant difference of the risk of the C allele in deceased cases when compared with that of alive ones (p > 0.05). In conclusion, the C allele (rs1800795) of IL-6 and the C allele (rs1800896) of IL-10 were highly significant in severe cases than in moderate cases. The C allele carriage of IL-6 showed only a significant difference between alive and deceased patients and not with the C allele of IL-10. [ABSTRACT FROM AUTHOR]

Aim: This study was undertaken to explicate the shared and distinctive genetic susceptibility and immune dysfunction in patients with T1D alone and T1D with CD (T1D + CD). Methods: A total of 100 T1D, 50 T1D + CD and 150 healthy controls were recruited. HLA-DRB1/DQB1 alleles were determined by PCR-sequence-specific primer method, SNP genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP-array and genotyping for INS-23 Hph1 A/T was done by RFLP. Autoantibodies and cytokine estimation was done by ELISA. Immune-regulation was analysed by flow-cytometry. Clustering of autoantigen epitopes was done by epitope cluster analytical tool. Results: Both T1D alone and T1D + CD had a shared association of DRB1*03:01, DRB1*04, DRB3*01:07/15 and DQB1*02. DRB3*01:07/15 confers the highest risk for T1D with relative risk of 11.32 (5.74–22.31). Non-HLA gene polymorphisms PTPN22 and INS could discriminate between T1D and T1D + CD. T1D + CD have significantly higher titers of autoantibodies, expression of costimulatory molecules on CD4 and CD8 cells, and cytokine IL-17A and TGF-β1 levels compared to T1D patients. Epitopes from immunodominant regions of autoantigens of T1D and CD clustered together with 40% homology. Conclusion: Same HLA genes provide susceptibility for both T1D and CD. Non-HLA genes CTLA4, PTPN22 and INS provide further susceptibility while different polymorphisms in PTPN22 and INS can discriminate between T1D and T1D + CD. Epitope homology between autoantigens of two diseases further encourages the two diseases to occur together. The T1D + CD being more common in females along with co-existence of thyroid autoimmunity, and have more immune dysregulated state than T1D alone. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a chronic, gynecological disorder, and the disease's pathogenesis is still debatable. Genes related to apoptosis have been revealed to be deregulated in endometriosis. Objective: This study investigates the relationship between polymorphic variants of Bax -248G>A and Bcl-2 -938C>A promoter regions with endometriosis risk in an Iranian population. Materials and Methods: In this case-control study, the polymorphisms of Bax -248G>A and Bcl-2 -938C>A promoter regions were analyzed in 127 Iranian cases and 125 controls who were referred to Ali-ibn-Abi Taleb Educational hospital, Zahedan, Iran between May 2022 and February 2023. The genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequencies of mutant allele A carriers and the A allele of Bax -248G>A polymorphism showed about 2-fold significant increase of endometriosis risk (p = 0.04; p = 0.01, respectively). The frequencies of the mutant genotype AA and A allele carriers of Bcl-2 -938C>A polymorphism were approximately 4 and 2.5-fold higher in endometriosis compared to the control women, which were highly significant (p > 0.001). Moreover, the allele A frequency of Bcl-2 -938C>A was associated with a 2-fold higher risk of endometriosis (p > 0.001). Furthermore, the combination effects of these 2 single nucleotide polymorphisms showed that women with Bax -248G>A GG and Bcl-2 -938C>A AA variant alleles were associated with about 5 times higher risk of endometriosis (p > 0.001). Notably, a significant difference was observed in mutant allele distribution between minimal/mild (stage I and II) and moderate/severe (stage III and IV) women with endometriosis disease. Conclusion: The results of our study provide evidence that Bcl-2 -938C>A and Bax -248G>A single nucleotide polymorphisms might be associated with the risk of endometriosis. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is renowned as a prominent cause of visual impairment worldwide. The association between manganese superoxide dismutase (MnSOD) gene, Ala16Val (rs4880), and DR susceptibility in people with type 2 diabetes mellitus (T2DM) remains contentious. Objective: This meta-analysis aims to evaluate risk of DR in T2DM patients with MnSOD Ala16Val polymorphism. Methods: A literature search was conducted using MEDLINE, Scopus, Web of Science, ScienceDirect, EMBASE, and grey literature to identify potential studies assessing the link between MnSOD polymorphism and DR risk among T2DM patients. The data was further analyzed in fixed/random effect models using RevMan 5.3 under five genetic models. Results: Six studies comprising 2,132 subjects from four distinct ethnicities were included. The present study revealed that MnSOD gene polymorphism was associated with a significantly increasing DR risk in T2DM patients under the co-dominant model (VV vs. AA) (OR 1.87 [1.42, 2.46], p<0.0001) and dominant model (VV+AV vs. AA) (OR 1.85 [1.02, 3.33], p=0.0400). Conclusions: T2DM individuals with rs4880 VV alleles are more susceptible to DR development, making them as a potential marker for heightened DR susceptibility in T2DM patients, laying the foundation for a gene panel to assess their susceptibility to develop DR. [ABSTRACT FROM AUTHOR]

Simple Summary: The shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) has been implicated in prion disease biology. Here, we identified the SPRN gene sequence and characterized its genetic polymorphisms in ducks. As a result, the duck and chicken Sho amino acid sequences shared 100% identity. Notably, we found an abundance of single nucleotide polymorphisms in the open reading frame of duck SPRN gene, which is comparable to those in prion disease-susceptible species. To date, there has been no evidence of prion disease in ducks to our knowledge. Given that our previous study on the duck prion protein gene suggested several characteristics of potential prion disease susceptibility, this study supports the need for additional experiments to examine the risk of developing prion diseases in ducks. Prion diseases are fatal neurodegenerative disorders characterized by an accumulation of misfolded prion protein (PrPSc) in brain tissues. The shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is involved in prion disease progress. The interaction between Sho and PrP accelerates the PrPSc conversion rate while the SPRN gene polymorphisms have been associated with prion disease susceptibility in several species. Until now, the SPRN gene has not been investigated in ducks. We identified the duck SPRN gene sequence and investigated the genetic polymorphisms of 184 Pekin ducks. We compared the duck SPRN nucleotide sequence and the duck Sho protein amino acid sequence with those of several other species. Finally, we predicted the duck Sho protein structure and the effects of non-synonymous single nucleotide polymorphisms (SNPs) using computational programs. We were the first to report the Pekin duck SPRN gene sequence. The duck Sho protein sequence showed 100% identity compared with the chicken Sho protein sequence. We found 27 novel SNPs in the duck SPRN gene. Four amino acid substitutions were predicted to affect the hydrogen bond distribution in the duck Sho protein structure. Although MutPred2 and SNPs&GO predicted that all non-synonymous polymorphisms were neutral or benign, SIFT predicted that four variants, A22T, G49D, A68T, and M105I, were deleterious. To the best of our knowledge, this is the first report about the genetic and structural characteristics of the duck SPRN gene. [ABSTRACT FROM AUTHOR]