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Background Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. Methods In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction–restriction fragment length polymorphism method. Results The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P >.05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P =.036, odds ratio = 2.09 [95% CI = 1.31-5.95]). Conclusions We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies. [ABSTRACT FROM AUTHOR]

Objective Idiopathic inflammatory myopathies (IIM) are a heterogeneous and life-threatening group of diseases; in particular, anti-melanoma differentiation-associated gene 5 antibody positive DM (MDA5+ DM) is reportedly strongly associated with high mortality rate. Tacrolimus (TAC) provides an excellent therapeutic option, but the trough concentration (Cmin)–outcome relationship remains unexplored. This study was undertaken to identify optimal Cmin and individualized dose based on CYP3A5 genotype for IIM patients. Methods A total of 134 IIM patients with 467 Cmin were enrolled. We examined the relationship between TAC Cmin and relapses. The receiver operating characteristic analysis was used to confirm the optimal Cmin. Analyses of factors influencing Cmin were conducted. The dose requirement based on CYP3A5 genotype was confirmed. Results TAC Cmin is strongly associated with relapses. The optimal cutoff values were 5.30, 5.85, 4.85 and 5.35 ng/ml for acute, subacute, chronic and all-phase IIM patients (P   =  0.001, 0.013, 0.002 and <0.001, respectively), as well as 5.35, 5.85, 5.55 and 5.85 ng/ml for acute, subacute, chronic and all-phase MDA5+ DM patients (P   =  0.007, 0.001, 0.036 and <0.001, respectively). CYP3A5 genotype was one of the significant factors influencing TAC Cmin. CYP3A5 expressers required 0.059 mg/kg/day to attain the target Cmin, while nonexpressers required 0.046 mg/kg/day (P   =  0.019). Conclusion TAC treatment may elicit favorable outcome in patients with IIM and MDA5+ DM when Cmin exceeded 5.35 and 5.85 ng/ml, which is crucial to a lower relapse rate. The individualized dose based on the CYP3A5 genotype provides a reference for TAC personalized therapy in IIM. [ABSTRACT FROM AUTHOR]

Introduction: Genetic factors play an important role in the etiopathogenesis of autism spectrum disorder (ASD). The Pogo Transposable Element with ZNF Domain protein (POGZ) gene (MIM*614787) has been reported to be one of the most frequently mutated genes associated with ASD. This study aims to analyze the exonic regions of the POGZ gene in individuals diagnosed with non-syndromic ASD. Methods: Fifty-one non-syndromic cases diagnosed with ASD according to the DSM-V diagnostic criteria, aged 2-18 years, were included in the study. The healthy control group consisted of 50 children of similar age groups without neurodevelopmental problems. Amplicons produced using deep intronic primers covering the mRNA-encoded regions of the POGZ gene from at least 50 base pairs were sequenced by Next Generation Sequencing Analysis. Results: No pathogenic or likely pathogenic variants reported in open-access databases (ClinVar, HGMD, etc.) were detected in the case group. In the ASD and healthy control groups, rs113396244, rs11204811, rs779479223, rs772352054, rs3831142, rs112072925, rs227453 and rs142860188 variants were determined. The rs3831142, rs112072925, rs2274535, rs142860188 variants were found statistically significant in the ASD group. The distribution of the cases with detected single nucleotide polymorphisms (SNPs) according to gender was not statistically significant. Conclusion: The variants identified as statistically significant within the patient group are situated in regions that encompass both the HP1-ZNF and DDE domains of the protein. Given the crucial role that the DDE domain plays, particularly in fetal brain development and neurogenesis, these four variants may potentially possess modifying and/or predisposing effects in the context of ASD. [ABSTRACT FROM AUTHOR]

Background: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. Methods: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. Results: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. Conclusions: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite instability (MSI) is crucial in colorectal cancer (CRC) due to deficient mismatch repair (MMR), often caused by MLH1 and MSH2 loss of function. This defect affects microsatellite loci globally. Recently, MSI at tetranucleotide loci has been identified as a distinct entity, potentially arising from isolated MSH3 loss of function due to its translocation to the cytoplasm under interleukin-6 (IL-6) influence. This study examined the impact of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on MSI types in sporadic CRC. A significant difference in gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was found, with the C allele being less common in tumors with di- and tetranucleotide instability (related to isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 may influence the IL-6 pathway, leading to MSI linked to MSH3 loss of function. Microsatellite instability (MSI) has been recognized as an important factor in colorectal cancer (CRC). It arises due to deficient mismatch repair (MMR), mostly attributed to MLH1 and MSH2 loss of function leading to a global MMR defect affecting mononucleotide and longer microsatellite loci. Recently, microsatellite instability at tetranucleotide loci, independent of the global MMR defect context, has been suggested to represent a distinct entity with possibly different consequences for tumorigenesis. It arises as a result of an isolated MSH3 loss of function due to its translocation from the nucleus to the cytoplasm under the influence of interleukin-6 (IL-6). In this study the influence of MSH3 and IL-6 signaling pathway polymorphisms (MSH3 exon 1, MSH3+3133A/G, IL-6-174G/C, IL-6R+48892A/C, and gp130+148G/C) on the occurrence of different types of microsatellite instability in sporadic CRC was examined by PCR–RFLP and real-time PCR SNP analyses. A significant difference in distribution of gp130+148G/C genotypes (p = 0.037) and alleles (p = 0.031) was observed in CRC patients with the C allele being less common in tumors with di- and tetranucleotide instability (isolated MSH3 loss of function) compared to tumors without microsatellite instability. A functional polymorphism in gp130 might modulate the IL-6 signaling pathway, directing it toward the occurrence of microsatellite instability corresponding to the IL-6-mediated MSH3 loss of function. [ABSTRACT FROM AUTHOR]

Common and tartary buckwheat are important cultivated species of the genus Fagopyrum. Genetic polymorphism of thirty-five genotypes of common buckwheat (Fagopyrum esculentum Moench) and tartary buckwheat (Fagopyrum tataricum Gaertn.) was analyzed using 10 random amplified polymorphic DNA (RAPD) primers. A total of 119 DNA fragments were amplified using ten RAPD primers with an average of 11.9 fragments per primer. The number of amplified fragments ranged from 6 (OPB-08) to 16 (SIGMA-D-01). PIC values ranged from 0.782 (OPC-08) to 0.919 (SIGMA-D-01) with an average of 0.871 per primer. The marker index (10.364) and diversity detecting index (2.961) were high and presented the utility of used marker technique. To evaluate the genetic relationships among buckwheat genotypes a phylogenetic tree based on UPGMA algorithm was constructed. The genotypes of common and tartary buckwheat were separated independently into cluster I and II. Cluster I separated 14 genotypes of tartary buckwheat into two subclusters (Ia, Ib). Genotype 903016, which originated in Pakistan, was separated individually into the subcluster Ia. Cluster II included genotypes of common buckwheat and was further subdivided into subcluster IIa and IIb. Two genotypes of subcluster IIb (Bamby and Hruszowska) were genetically the closest. Bamby and Hruszowska reflected the maximum similarity value (0.605) according to Jaccard's coefficient of similarity. Based on the presented data it is suggested that the RAPD technique is suitable for differentiation among genotypes of common and tartary buckwheat. RAPD primers have proven to be reliable and useful method for studying genetic variability of buckwheat genotypes. [ABSTRACT FROM AUTHOR]

Voriconazole is the first‐line treatment for invasive aspergillosis. Its pharmacokinetics exhibit considerable inter‐ and intra‐individual variability. The purpose of this study was to investigate the effects of CYP2C19, CYP2C9, CYP3A4, and FMO3 genetic polymorphisms and sex on the pharmacokinetics of voriconazole in healthy Chinese adults receiving single‐dose and multiple‐dose voriconazole, to provide a reference for its clinical individualized treatment. A total of 123 healthy adults were enrolled in the study, with 108 individuals and 15 individuals in the single‐dose and multiple‐dose doses, respectively. Plasma voriconazole concentrations were measured using a validated LC‐MS/MS method, and pharmacokinetics parameters were calculated using the non‐compartmental method with WinNonlin 8.2. CYP2C19, CYP2C9, CYP3A4, and FMO3 single‐nucleotide polymorphisms were sequenced using the Illumina Hiseq X‐Ten platform. The results suggested that CYP2C19 genetic polymorphisms significantly affected the pharmacokinetics of voriconazole at single doses of 4, 6, and 8 mg/kg and multiple doses of voriconazole. CYP3A4 rs2242480 had a significant effect on AUC0‐∞ (area under the plasma concentration‐time curve from time 0 to infinity) and MRT (mean residence time) of voriconazole at a single dose of 4 mg/kg in CYP2C19 extensive metabolizer. Regardless of the CYP2C19 genotype, CYP2C9 rs1057910 and FMO3 rs2266780 were not associated with the pharmacokinetics of voriconazole at three single‐dose levels or multiple doses. No significant differences in most voriconazole pharmacokinetics parameters were noted between male and female participants after single and multiple dosing. For patients receiving voriconazole treatment, CYP2C19 genetic polymorphisms should be genotyped for its precision administration. In contrast, based on our study of healthy Chinese adults, it seems unnecessary to consider the effects of CYP2C9, CYP3A4, and FMO3 genetic polymorphisms on voriconazole pharmacokinetics. [ABSTRACT FROM AUTHOR]

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case–control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non‐DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real‐time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC. Methods: This research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics. Results: In comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers. Conclusion: Individuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the longitudinal evolution of vertical jump height in soccer players and its association with their genotypic profiles. The genotypes of 37 soccer players were characterized and the countermovement jump (CMJ) height, concentric mean power, force, and jump strategy were assessed at two time points: at the onset of the regular season (Pre) and at the conclusion of the first half (Mid). AMPD1 (rs17602729), ACE (rs4646994), ACTN3 (rs1815739), CKM (rs8111989), and MLCK (rs2849757 and rs2700352) polymorphisms were genotyped. No significant differences were found between Pre and Mid in concentric power (p = 0.068; d = 0.08) or force (p = 0.258; d = 0.04), while jump height displayed trivial increases (p = 0.046; d = 0.15). Individual analysis revealed that 38% of participants increased the vertical jump height and mean concentric power over the smallest worthwhile change (SWC), while 27% experienced an increased mean concentric force. The positive responders were characterized by a decreased frequency of the AA genotype and an increased frequency of the CA genotype for the c.37885C>A polymorphism of MLCK (p = 0.035), as well as a decreased frequency of the TT genotype of ACTN3 (p = 0.042) and the CC genotype of AMPD1 (p = 0.022). Our findings suggest that genetic analysis could explain some variability in neuromuscular adaptations during the in-season. [ABSTRACT FROM AUTHOR]

Background: This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy's development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF. Methods: In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping. Results: The study's patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development. Conclusions: Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Following the coronavirus disease 2019 outbreak (COVID-19), it became a worrisome health burden worldwide. COVID-19-associated mucormycosis emergence, characterized by dysregulated inflammation and iron metabolism, exacerbated the prognosis of affected patients. Given the significance of hepcidin in regulating inflammation and iron metabolism, this study investigated the significance of hepcidin single nucleotide polymorphisms (SNP) in COVID-19-associated mucormycosis development, along with the association between the clinical and laboratory factors and COVID-19-associated mucormycosis. Methods: From September 2021 to November 2021, COVID-19 patients with and without mucormycosis were enrolled in this cross-sectional study. Their medical records and laboratory results were investigated. SNP genotyping was performed using Sanger sequencing. Hardy-Weinberg Equilibrium, Pearson's Chi square, and student t test were used for analyzing the data using SPSS software version 25. P<0.05 was regarded as statistically significant. Results: Here, 110 COVID-19 patients with and without mucormycosis were investigated. Elevated levels of urea, aspartate aminotransferase, lactate dehydrogenase, and increased ratio of polymorphonuclear neutrophil to lymphocytes were associated with decreased risk of COVID-19-associated mucormycosis in patients (all P<0.05). Moreover, diabetes mellitus increased the risk of mucormycosis (P=0.028). In contrast to patients without mucormycosis, patients with mucormycosis did not display 442 GA and SNP335 GT genotypes. Unlike patients without mucormycosis, none of the patients with mucormycosis had SNP442 GA and SNP335 GT genotypes. Regarding SNP 443 C>T, and the combination of SNPs 582 A>G and 443 C>T, CC genotype and AA+CC genotypes were associated with increased lactate dehydrogenase levels in COVID-19 patients, respectively. Conclusion: Regarding SNP 443 C>T, the CC genotype was associated with increased lactate dehydrogenase levels in COVID-19 patients. In terms of SNP 582 A>G and SNP 443 C>T, COVID-19 patients with AA+CC genotypes had higher levels of LDH. None of the patients with mucormycosis had SNP442 GA and SNP335 GT genotypes. [ABSTRACT FROM AUTHOR]

Background: The methylenetetrahydrofolate reductase (MTHFR) gene is an essential gene in the metabolism of folate-homocysteine. Recently, the level of homocysteine was found to be a significant marker in the follow-up of COVID-19 infection. Thus, this study aimed to detect the effect of genetic polymorphisms for single nucleotide polymorphisms (SNPs) (c.66A>G, c.1298A>C, and c.677CT) on COVID-19 infection. Methods: Blood samples were collected from 270 patients with COVID-19 in the medical center of Al-Shifa (Baghdad, Iraq) from November 2020 to March 2021. Tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMSPCR) technique was used for the detection of genotypes of SNPs. The odds ratio (OR) was used to detect the relationship between SNPs and COVID-19 infections. Haplotype analysis was performed by SHEsis software. Results: There was a significant difference between mild/ moderate cases and severe/critical cases for ages (35-45), (46-55), and (56-65) years (P<0.0001, P=0.01, and P=0.006, respectively). The results showed significant differences in the T allele for SNP c.677>C (P<0.0001 and OR=4.58). The C allele for SNP c.1298A>C indicated significant differences (P<0.001 and OR=3.15). Besides, the G allele for SNP c.677C>T showed significant differences (P<0.001 and OR=6.64). Consequently, these SNPs showed a predisposition to the development of COVID-19 infection. With regard to the C-A-A, T-A-A and T-C-G haplotypes indicated significant differences between the control and patient groups. The C-A-A was related to a decreased risk and indicated a protective effect against COVID-19 infection development (P<0.0001 and OR=0.218). The increased risk was associated with T-A-A and T-C-G haplotypes and indicated the risk impact on COVID- 19 infection development (P<0.0001, P=0.004, and OR=15.5, OR=6.772, respectively). Furthermore, the linkage disequilibrium (LD) for SNPs was studied, and the complete D' value was 99%. Conclusion: The genetic polymorphisms of SNPs (c.66A>G, c.1298A>C, and c.677C>T) in the Iraqi population were associated with COVID-19 infection. [ABSTRACT FROM AUTHOR]

Purpose: To study the correlations of genetic variants of telbivudine phosphorylase kinases and telbivudine plasma concentration with creatine kinase elevation in chronic hepatitis B patients who received telbivudine. Methods: An observational study was performed in China chronic hepatitis B patients receiving telbivudine therapy at 600 mg once daily. Plasma concentration was measured 12 h after taking telbivudine using ultra-performance liquid chromatography–tandem mass spectrometry and SNPs located in RRM2B, TK2, and NME4 was detected by MALDI-TOF mass spectrometry. All statistical analyses were performed with R 4.3.1 and all graphs were drawn by Origin 2023b and P value < 0.05 was considered statistically significant. Results: A total of 140 patients receiving telbivudine therapy were recruited with a median plasma concentration of 952.49 (781.07–1238.98) ng/mL. The value of plasma concentration was proportional to the grade of creatine kinase elevation and the best telbivudine plasma concentration threshold to discriminate the grade 3/4 CK elevation was 1336.61 ng/mL. Multivariate analysis revealed that plasma concentration and rs3826160 were the independent risk factor of telbivudine-induced creatine kinase elevation. Patients with TC and CC genotype in rs3826160 not only had a higher incidence of creatine kinase elevation but also a higher plasma concentration than TT genotype carriers. Conclusion: Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase. [ABSTRACT FROM AUTHOR]

Characterizing spatial patterns in allele frequencies is fundamental to evolutionary biology because these patterns contain evidence of underlying processes. However, the spatial scales at which gene flow, changing selection, and drift act are often unknown. Many of these processes can operate inconsistently across space, causing nonstationary patterns. We present a wavelet approach to characterize spatial pattern in allele frequency that helps solve these problems. We show how our approach can characterize spatial patterns in relatedness at multiple spatial scales, i.e. a multilocus wavelet genetic dissimilarity. We also develop wavelet tests of spatial differentiation in allele frequency and quantitative trait loci (QTL). With simulation, we illustrate these methods under different scenarios. We also apply our approach to natural populations of Arabidopsis thaliana to characterize population structure and identify locally adapted loci across scales. We find, for example, that Arabidopsis flowering time QTL show significantly elevated genetic differentiation at 300–1,300 km scales. Wavelet transforms of allele frequencies offer a flexible way to reveal geographic patterns and underlying evolutionary processes. [ABSTRACT FROM AUTHOR]

Background: The Lewis (Le) blood group system, unlike most other blood groups, is not defined by antigens produced internally to the erythrocytes and their precursors but rather by glycan antigens adsorbed on to the erythrocyte membrane from the plasma. These oligosaccharides are synthesized by the two fucosyltransferases FUT2 and FUT3 mainly in epithelial cells of the digestive tract and transferred to the plasma. At their place of synthesis, some Lewis blood group carbohydrate antigen variants also seem to be involved in various gastrointestinal malignancies. However, relatively little is known about the transcriptional regulation of FUT2 and FUT3. Summary: To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for FUT2 and FUT3 and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase FUT2 and FUT3 transcription and translation upon interaction. Key Messages: Understanding the regulation of FUT2 and FUT3 is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases. Plain Language Summary: The Lewis (Le) blood group system, in contrast to the majority of blood groups, is not able to synthesize its antigens itself. It depends on the attachment of different oligosaccharides to the erythrocyte membrane, which are adsorbed from the plasma. These glycans are modified by the fucosyltransferases 2 and 3 enzymes (FUT2/3). Beside their role in defining the Lewis blood group, FUT2 and FUT3 are also known to be involved in the susceptibility and progression of various gastrointestinal pathologies, like inflammatory bowel diseases (IBD) or colorectal cancer (CRC). Even though different expression levels of FUT2 and FUT3 have been described in these malignancies, relatively little is known about the mechanisms behind their transcriptional regulation. In this review, we aim to shed light on transcription factors (TFs) responsible for FUT2 and FUT3 expression as well as on post-transcriptional regulators by the means of RNA binding proteins (RBPs) and microRNAs (miRNAs). To achieve our goal, we combined previous knowledge on FUT2 and FUT3 expression regulation with a computational analysis to predict additional novel regulators. On this way, we are able to broaden our knowledge on FUT2 and FUT3 expression regulation and consequently might be able to transfer our findings into diagnostics or therapeutics in the future. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate for associations between the occurrence of palpitations reported by women prior to breast cancer surgery and single nucleotide polymorphisms (SNPs) for neurotransmitter genes. SAMPLE & SETTING: A total of 398 women, who were scheduled for unilateral breast cancer surgery, provided detailed information on demographic and clinical characteristics and the occurrence of palpitations prior to breast cancer surgery. METHODS & VARIABLES: The occurrence of palpitations was assessed using a single item (i.e., "heart races/pounds" in the past week ["yes"/"no"]). Blood samples were collected for genomic analyses. Multiple logistic regression analyses were used to identify associations between the occurrence of palpitations and variations in neurotransmitter genes. RESULTS: Nine SNPs and two haplotypes among 11 candidate genes were associated with the occurrence of palpitations. These genes encode for a number of neurotransmitters and/or their receptors, including serotonin, norepinephrine, dopamine, gammaamino butyric acid, Substance P, and neurokinin. IMPLICATIONS FOR NURSING: These findings suggest that alterations in a variety of neurotransmitters contribute to the development of this symptom. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer remains a burden for women worldwide. Among the factors that contribute to breast cancer development is estrogen exposure during one's lifetime, both endocrine and exocrine. Polymorphisms in KEAP1-NRF2 complex, the master regulator of oxidative stress metabolism, have been correlated with a poorer outcome. The aim of our study was to identify and correlate polymorphisms in this complex, in breast cancer tissue, benign surrounding tissue and in peripheral blood. We verified a tendency towards the loss of heterozygosity in the benign surrounding tissue when compared to blood and to tumour tissue. Correlating with clinical data, histologic grade 2 has a higher variability of genotypes. The results indicate a heterogeneous and active microenvironment. Therefore, clinical approaches would benefit from the evaluation of somatic mutations in this complex. Moreover, further studies should be developed in order to evaluate the predictive value of the histologic grades, taking into consideration the genetic profile. Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions. [ABSTRACT FROM AUTHOR]

Aims Alcohol drinking is associated with central obesity, hypertension, and hyperlipidemia, which further causes metabolic syndrome (MetS). However, prior epidemiological studies on such associations lack experimental evidence for a causal relationship. This study aims to explore the causal relationship between drinking behavior and MetS in Taiwan population by using Mendelian randomization (MR) analysis. Methods A cross-sectional study was conducted using the Taiwan Biobank database, which comprised 50 640 Han Chinese who were 30–70 years old without cancer from 2008 to 2020. In MR analysis, we constructed weighted and unweighted genetic risk scores by calculating SNP alleles significantly associated with alcohol drinking. We calculated odds ratios and 95% confidence interval (CI) by using a two-stage regression model. Results A total of 50 640 participants were included with a mean age of 49.5 years (SD: 1.67 years), 36.6% were men. The adjusted odds ratio (aOR) of MetS per 5% increase in the likelihood of genetic predisposition to drink based on weighted genetic risk score with adjustment was 1.11 (95% CI: 1.10, 1.12, P  < .001). Analysis was also conducted by grouping the likelihood of genetic predisposition to drink based on quartiles with multivariate adjustment. Using Q1 as the reference group, the aORs of MetS for Q2, Q3, and Q4 were 1.19 (1.12, 1.27, p  < .001), 1.31 (1.23, 1.40, p  < .001), and 1.87 (1.75, 2.00, p  < .001), respectively, for the weighted genetic risk score. Conclusions This study shows a modest relationship between drinking behavior and MetS by using MR analysis. [ABSTRACT FROM AUTHOR]

• Cycling time trial decreases after caffeine supplementation intake. • Cycling performance is affected by CYP1A2 genotype. • Acute caffeine intake improves cycling time trial only in individuals with A allele. • Wingate and CMJ performance does not change after caffeine supplementation, irrespective of genotype. The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The genetic variation of a specific gene, human cytochrome P450 enzyme 1A2 (CYP1A2) (rs762551), may be one reason for this difference. This systematic review and meta-analysis aimed to comprehensively evaluate the influence of CYP1A2 gene types on athletes' exercise performance after caffeine intake. A literature search through 4 databases (Web of Science, PubMed, Scopus, and China National Knowledge Infrastructure) was conducted until March 2023. The effect size was expressed as the weighted mean difference (WMD) by calculating fixed effects meta-analysis if heterogeneity was not significant (I 2 ≤ 50% and p ≥ 0.1). Subgroup analyses were performed based on AA and AC/CC genotype of CYP1A2. The final number of studies meeting the inclusion criteria was 12 (n = 666 participants). The overall analysis showed that the cycling time trial significantly improved after caffeine intake (WMD = –0.48, 95% confidence interval (95%CI): –0.83 to –0.13, p = 0.007). In subgroup analyses, acute caffeine intake improved cycling time trial only in individuals with the A allele (WMD = –0.90, 95%CI: –1.48 to –0.33, p = 0.002), but not the C allele (WMD = –0.08, 95%CI: –0.32 to 0.17, p = 0.53). Caffeine supplementation did not influence the Wingate (WMD = 8.07, 95%CI: –22.04 to 38.18, p = 0.60) or countermovement jump test (CMJ) performance (WMD = 1.17, 95%CI: –0.02 to 2.36, p = 0.05), and these outcomes were not influenced by CYP1A2 genotype. Participants with the CYP1A2 genotype with A allele improved their cycling time trials after caffeine supplementation. However, compared to placebo, acute caffeine supplementation failed to increase the Wingate or CMJ performance, regardless of CYP1A2 genotype. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ilam University of Medical Sciences is the property of Ilam University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Aim: Hematotoxicity is a lifethreatening condition that has become the major cause of drug discontinuation in patients with acute lymphoblastic leukemia (ALL). The nudix hydrolase 15 (NUDT15) gene polymorphism (c.415C>T) is reported to have an association with the hematotoxicity of 6-mercaptopurine (6-MP) as maintenance therapy in patients with ALL. However, the prevalence of this genetic polymorphism in the Indonesian population is unknown. This study aimed to assess the frequency of NUDT15 polymorphism among Indonesian pediatric patients with ALL and its association with the hematotoxicity of 6-MP. Patients and Methods: A total of 101 stored DNA samples from pediatric patients with ALL receiving 6-MP treatment were used for genetic testing. Direct sequencing was conducted to determine the NUDT15 c.415C>T genotype. Chi-square or Fisher's exact test were employed to examine the association between the NUDT15 c.415C>T genotype and hematotoxicity. Results: All (100%) of the DNA samples from patients with ALL treated with 6-MP exhibited a homozygous variant of the NUDT15 c.415C>T genotype, 70.3% of which showed hematotoxicity to some extent. We found no significant differences in NUDT15 gene polymorphism among patients with ALL with different states of hematotoxicity. Conclusion: The observed high frequency of NUDT15 c.415C>T in our study population might explain the elevated prevalence of 6-MPassociated hematotoxicity in pediatric patients with ALL within the Indonesian population. Our study provides new insight regarding the NUDT15 gene polymorphism and its relation to hematotoxicity. Further studies are required to determine the necessity of adjusting the initial dose of 6-MP for Indonesian pediatric patients with ALL. [ABSTRACT FROM AUTHOR]

Copyright of Acta Agriculturae Zhejiangensis is the property of Acta Agriculturae Zhejiangensis Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aim: Celiac disease (CD) has proinflammatory and pathogenic immune responses to gluten in intestinal tissue, leading to structural changes in the mucosa of the small intestine. The association of human leukocyte antigen (HLA)‐DQ2 and DQ8 genotypes with CD has been previously reported. This test has a negative predictive value close to 100%, so its main purpose is to rule out the detection of CD completely or almost completely. There is limited information regarding HLA‐DQ4/5 in CD. This study was conducted to determine the HLA‐DQ4/5 genotypes in a group of Southwestern Iranian children with CD. Methods: We conducted a case‐control study in Southwest Iran involving 100 participants, employing a nonprobabilistic sampling method. Samples were taken from participants' oral buccal mucosa at Imam Sajjad Hospital of Yasuj, Iran. Then DNA was extracted from these samples and used to determine the frequency of HLA‐DQ4/5 genotypes through Sequence‐Specific Primer‐Polymerase Chain Reaction assay. SPSS 20 was utilized for statistical analyses. Results: Fifty diagnosed patients with CD (high anti‐tissue transglutaminase [tTG]‐IgA level [upper limit of normal] with pathological findings of Marsh III) and 50 non‐CD individuals (normal anti‐tTG‐IgA level and normal total IgA level) were enrolled in the study from August 5, 2022 to October 15, 2023. Findings showed that the DQ4a*4b allele has the highest frequency in the CD samples (78%, p < 0.01) followed by the DQ5a*5b allele (12%, p < 0.01). Additionally, there was a higher prevalence of DQ4/DQ5 in patients with CD compared to controls (odds ratio = 6.5, confidence interval = 0.84 to 69.46, p < 0.01). Furthermore, a significant association was found among HLA DQ4/5 genotype, age (>9.5) (p < 0.01), and gender (female) (p < 0.05). Conclusion: The observed significant differences among HLA‐DQ4 and HLA‐DQ5 in Iranian CD samples against controls and the high value of the relative risks showed the significant function of the studied alleles in the prevalence of CD in Iranian patients. [ABSTRACT FROM AUTHOR]

Background and Aims: To further substantiate the role of antibody‐mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane‐bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course. Methods: We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of CD46, CD55, and CD59 in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters. Results: The genotype frequencies of rs28371582, a 21‐bp deletion in the CD55 promotor region, were altered in patients with MMN as compared to controls (p.009; Del/Del genotype 16.8% vs. 7.7%, p.005, odds ratio: 2.43 [1.27–4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040–0.490, p.019). The presence of CD59 rs141385724 was associated with less severe pre‐diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083–1.80, p.032). Interpretation: MMN susceptibility is associated with a 21‐bp deletion in the CD55 promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long‐term disease outcome. Taken together, these results point out the relevance of the pre‐C5 level of the complement cascade in the inflammatory processes underlying MMN. [ABSTRACT FROM AUTHOR]

The rate at which beneficial alleles fix in a population depends on the probability of and time to fixation of such alleles. Both of these quantities can be significantly impacted by population subdivision and limited gene flow. Here, we investigate how limited dispersal influences the rate of fixation of beneficial de novo mutations, as well as fixation time from standing genetic variation. We investigate this for a population structured according to the island model of dispersal allowing us to use the diffusion approximation, which we complement with simulations. We find that fixation may take on average fewer generations under limited dispersal than under panmixia when selection is moderate. This is especially the case if adaptation occurs from de novo recessive mutations, and dispersal is not too limited (such that approximately F ST < 0.2 ⁠). The reason is that mildly limited dispersal leads to only a moderate increase in effective population size (which slows down fixation), but is sufficient to cause a relative excess of homozygosity due to inbreeding, thereby exposing rare recessive alleles to selection (which accelerates fixation). We also explore the effect of metapopulation dynamics through local extinction followed by recolonization, finding that such dynamics always accelerate fixation from standing genetic variation, while de novo mutations show faster fixation interspersed with longer waiting times. Finally, we discuss the implications of our results for the detection of sweeps, suggesting that limited dispersal mitigates the expected differences between the genetic signatures of sweeps involving recessive and dominant alleles. [ABSTRACT FROM AUTHOR]

Objective: The Arab Gulf is highly vulnerable to T2DM and its serious consequences. The manner in which these populations respond to such alterations in their surroundings may largely be governed by their genetic makeup. This review aimed to screen the genetic loci candidates that are associated with T2DM to assess the most prominent one in the early diagnosis of this chronic dysfunction. Methods: Variable pieces of literature were searched to assess the association between pathogenic single-nucleotide polymorphisms (SNPs) and the onset of T2DM in the Arab Gulf countries. The effects of odd ratio (OR), sample sizes, and collaborations of the captured genes of the eligible studies were analyzed. The protocol was registered in National Institute for Health Research. Results: Twenty-seven pathogenic SNPs were identified in 16 genes that were reported in 31 articles encompassing 15,982 patients and 11,976 controls. The highest numbers of conducted research were localized in Iraq and Saudi Arabia with 39% and 32%, respectively. HNF4A and TCF7L2 genes represent the most extensively studied pathogenic genes in terms of the number of individuals included and the number of T2DM-related loci, respectively. Intron SNPs exhibited the highest percentages of pathogenic loci associated with T2DM with 61%. Moderate association between the pathogenic SNPs and disease outcome was observed, but strengths and weights of association vary across studies. Conclusion: For a better understanding of the molecular etiology of T2DM, finding SNPs, and establishing a meaningful genotype-phenotype connection for complicated diabetic disorders, the cumulative relevance of identified pathogenic SNPs in Arab Gulf was shown. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic beta cell destruction is a hallmark of type 1 diabetes (T1D), a heterogeneous disorder with a wide range of potential causes. T cell activation molecules have been shown to play an important role in the development of T1D, according to the majority of studies. Some autoimmune diseases have been linked to SNPs in the 4q27 region, specifically in the KIAA1109-interleukin 2 (IL2)-IL21 block. The purpose of this research was to look into how certain polymorphic variants in the 4q27 region are linked to T1D. Methods: We investigated whether variants in the 4q27 region could be a causal factor in T1D susceptibility. Polymorphisms of ten single-nucleotide polymorphisms (SNPs) belonging to the KIAA1109/IL21/IL2 block were studied in 255 individuals from 59 families using the Sequenom MassARRAY platform. Results: The IL21/IL2 region was found to have a significant association with T1D in Tunisian cohorts. We found that the T allele of the rs2221903 marker is disproportionately passed down from parents to their children. In addition, haplotype analyses encompassing all of the SNPs under consideration show that the GACAGGA and the shortly TT haplotypes were significantly over-transmitted from parents to their children, suggesting they may be a T1D genetic susceptibility factor in our population. Conclusion: Several autoimmune disorders (ADs) have been linked to the IL2/IL21 genes, suggesting that there is a shared genetic background that confers a common genetic predisposition across ADs. More research into the genetic and functional aspects of the 4q27 region is needed to better explain the role it plays in the risk of ADs. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study was to assess if there were differences in allelic and genotypic frequencies of a loss-of-function SNP of ADORA2A (rs2298383) and a gain-of-function single nucleotide polymorphism (SNP) of P2RX7 (rs208294) in the severity of SARS-CoV-2-associated infection. Fifty-five individuals were enrolled and categorized according to the severity of the infection. Endpoint genotyping was performed in blood cells to screen for both SNPs. The TT genotype (vs. CT + CC) and the T allele (vs. C allele) of P2RX7 SNP were found to be associated with more severe forms of COVID-19, whereas the association between ADORA2A SNP and the severity of infection was not significantly different. The T allele of P2RX7 SNP was more frequent in people with more than one comorbidity and with cardiovascular conditions and was associated with colorectal cancer. Our findings suggest a more prominent role of P2X7R rather than of A2AR polymorphisms in SARS-CoV-2 infection, although larger population-based studies should be performed to validate our conclusions. [ABSTRACT FROM AUTHOR]

Psoriasis is a disease caused by genetics and immune system dysfunction, affecting the skin and joints. Toll-like receptors (TLRs) play an important role in triggering the innate immune response and controlling adaptive immunity. The role of TLR2 in the progression of psoriasis is not well understood. A case-control study was conducted on a northern Chinese Han population, consisting of psoriasis patients and healthy control subjects. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls. Four TLR2 SNPs (rs11938228, rs4696480, rs3804099, rs5743699) were genotyped and found to be in linkage disequilibrium. The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model. The haplotypes ATTC and ATCC were found to be protective against psoriasis. Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China. [ABSTRACT FROM AUTHOR]

Copyright of Anbar Journal of Agricultural Sciences is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, the phylogenetic relationships and genetic structure of 10 collected genotypes of Artemisia szowitziana (Besser) Grossh and Artemisia fragrans Willd. species from different regions of Azerbaijan were investigated using RAPD primers. A total of 94 amplicons were amplified using selected RAPD primers. Among them 3 band with OPA-02 primers and 12 band with OPW-17 primers were amplified. The highest polymorphism among the investigated RAPD markers was 100, 90.91 and 90%, which has been obtained by OPW-17, OPT-19, and OPT-20 primers, respectively. However, the calculated average value of polymorphism was as high as 72.79% based on 10 different RAPD markers. The average PIC (Polymorphism Information Content) value (0.864) has indicated the rich genetic diversity among the studied samples. The cluster analyses by using Jaccard similarity index and UPGMA method classified all Artemisia L. samples into 6 major groups. Principal Component Analysis (PCA) justified 74.22% of the total variance. Based on the results obtained, it has been observed that there is a wide range of diversity in the molecular level between the population of Artemisia szowitziana (1-2 and 4-6 samples) and Artemisia fragrans (3, 5, 7 and 8, 9, 10 samples) and between population of the Artemisia species in Azerbaijan. [ABSTRACT FROM AUTHOR]

Objective: Musculoskeletal injuries mainly occur in tendons and ligaments and their aetiology is tightly connected with genetic and environmental influences. This review and meta-analysis identifies and evaluates the potential association of the COL5A1 rs12722 polymorphism with lower limb musculoskeletal injuries in adults (18-60 years). Methods: Literature database searching (SCOPUS, Web of Science and PubMed) and screening provided nine studies for analysis. Data was extracted and interpreted by main injury types focusing on the genotype distribution (CC, CT, TT) of the rs12722 polymorphism. Meta-analysis was carried out using different modes of inheritance and injury sub-groups. Results: Many individual studies indicated no significant difference between cases and controls (p>0.05), but pooled data showed significant association of COL5A1 rs12722 polymorphism with lower limb musculoskeletal risk of injury (p=0.009). The meta-analysis showed a significant effect for the total sample for the recessive model of inheritance (OR =1.28 (CI 1.03-1.57, p=0.021) and ACLI (OR=1.31 (CI 1.03-1.67, p=0.026). Conclusions: The systematic review and meta-analyses confirm that T allele carriers (TT, CT) were more susceptible to injury, while the C allele is protective, decreasing the risk of injury. Keywords: Col5A1 Gene, Meta-analysis, rs12722 Polymorphism, Musculoskeletal Injuries, Systematic reviewObjective: Musculoskeletal injuries mainly occur in tendons and ligaments and their aetiology is tightly connected with genetic and environmental influences. This review and meta-analysis identifies and evaluates the potential association of the COL5A1 rs12722 polymorphism with lower limb musculoskeletal injuries in adults (18-60 years). Methods: Literature database searching (SCOPUS, Web of Science and PubMed) and screening provided nine studies for analysis. Data was extracted and interpreted by main injury types focusing on the genotype distribution (CC, CT, TT) of the rs12722 polymorphism. Meta-analysis was carried out using different modes of inheritance and injury sub-groups. Results: Many individual studies indicated no significant difference between cases and controls (p>0.05), but pooled data showed significant association of COL5A1 rs12722 polymorphism with lower limb musculoskeletal risk of injury (p=0.009). The meta-analysis showed a significant effect for the total sample for the recessive model of inheritance (OR =1.28 (CI 1.03-1.57, p=0.021) and ACLI (OR=1.31 (CI 1.03-1.67, p=0.026). Conclusions: The systematic review and meta-analyses confirm that T allele carriers (TT, CT) were more susceptible to injury, while the C allele is protective, decreasing the risk of injury. [ABSTRACT FROM AUTHOR]

Objective. To study associations between polymorphic variants of the SLC6A4 gene and depression in people aged 25–44 years old in Novosibirsk. Materials and methods. The study was performed in 2013–2016 and included 403 men (mean age 34 ± 0.4 years, response rate 71%) and 531 women (mean age 35 ± 0.4 years, response rate 72%) from an open population of residents aged 25–44 years in the Oktyabrskii district of Novosibirsk. Depression was assessed using the MONICA-MOPSY psychosocial questionnaire. The study polymorphisms of the SLC6A4 gene were genotyped using the PCR-RFLP method. Results. Depression was present in 12.8% of people aged 25–44 years (8.9% in the male population and 15.8% in the female population); moderate levels of depression occurred in 24.5% of the population (21.3% of men and 26.9% of women) (χ2 = 17.071, df = 2, p < 0.001). The most common genotype of the SLC6A4 gene in people aged 25–44 years in Novosibirsk was SLA (43.3%), followed by LALA (26.4%) and then SS (17.8%); less common genotypes in people aged 25–44 years were LALG (6.9%), SLG (4.4%), and LGLG (1.4%). Carriage of the SLA genotype (52.5% and 62.9%) increased the chance of developing both an moderate level of depression, by a factor of 2.4 (95% CI 1.278–4.355), and depression in general, by a factor of 1.9 (95% CI 1.142–3.271), as compared with carriers of the LALA genotype (31.9% and 46.7%), (χ2 = 7.674, df = 1, p < 0.01 and χ2 = 6.095, df = 1, p < 0.05). Carriers of the LALG genotype (57.9%) also had a higher chance of developing a moderate level of depression (OR = 2.929 (95% CI 1.039–8.261)) than carriers of the LALA genotype (31.9%) (χ2 = 4.326, df = 1, p < 0.05) (p < 0.05). Conclusions. Associations between polymorphic variants of the SLC6A4 gene and depression were found. [ABSTRACT FROM AUTHOR]

Several single nucleotide polymorphisms (SNPs) in multiple interleukin receptor genes could be associated with asthma risk and/or phenotype. Interleukin-17 (IL-17) has been implicated in tissue inflammation and autoimmune diseases. As no previous studies have uncovered the potential role of IL17 receptor A (RA) gene variants in asthma risk, we aimed to explore the association of four IL17RA SNPs (i.e., rs4819554A/G, rs879577C/T, rs41323645G/A, and rs4819555C/T) with asthma susceptibility/phenotype in our region. TaqMan allelic discrimination analysis was used to genotype 192 individuals. We found that the rs4819554 G/G genotype significantly reduced disease risk in the codominant (OR = 0.15, 95%CI = 0.05–0.45, p < 0.001), dominant (OR = 0.49, 95%CI = 0.26–0.93, p = 0.028), and recessive (OR = 0.18, 95%CI = 0.07–0.52, p < 0.001) models. Similarly, rs879577 showed reduced disease risk associated with the T allele across all genetic models. However, the A allele of rs41323645 was associated with increased disease risk in all models. The G/A and A/A genotypes have higher ORs of 2.47 (95%CI = 1.19–5.14) and 3.86 (95%CI = 1.62–9.18), respectively. Similar trends are observed in the dominant 2.89 (95%CI = 1.47–5.68, p = 0.002) and recessive 2.34 (95%CI = 1.10–4.98, p = 0.025) models. For the rs4819555 variant, although there was no significant association identified under any models, carriers of the rs4819554*A demonstrated an association with a positive family history of asthma (71.4% in carriers vs. 27% in non-carriers; p = 0.025) and the use of relievers for >2 weeks (52.2% of carriers vs. 28.8% of non-carriers; p = 0.047). Meanwhile, the rs4819555*C carriers displayed a significant divergence in the asthma phenotype, specifically atopic asthma (83.3% vs. 61.1%; p = 0.007), showed a higher prevalence of chest tightness (88.9% vs. 61.5%; p = 0.029), and were more likely to report comorbidities (57.7% vs. 16.7%, p = 0.003). The most frequent haplotype in the asthma group was ACAC, with a frequency of 22.87% vs. 1.36% in the controls (p < 0.001). In conclusion, the studied IL17RA variants could be essential in asthma susceptibility and phenotype in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL. Methods: A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted. Results: There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92). Conclusions: Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL. [ABSTRACT FROM AUTHOR]

Previous research concerning the interplay between genetics and parenting in the development of the parent-child relationship during adolescence has been extremely scarce, predominantly adopting single-gene designs. This limited body of work has largely overlooked the distinct effects of maternal and paternal roles, as well as potential gender differences. Additionally, existing gene-by-environment (G × E) studies have mainly concentrated on adverse environmental factors and associated negative outcomes, somewhat neglecting positive environments and outcomes. The present study examined the interactions of cumulative genetic scores (CGS, dopamine receptor D2 TaqIA and oxytocin receptor gene rs53576 polymorphisms) with both positive and negative parenting on parent-adolescent cohesion and conflict. Furthermore, this study aimed to ascertain with which gene-environment model the potential G × E interactions would align. A total of 745 Chinese Han adolescents (Mage = 13.36 ± 0.96 years; 46.8% girls) from grades 7 to 9 participated in this study. Results revealed a significant effect of CGS and negative maternal parenting on mother-adolescent conflict among males, consistent with the weak differential susceptibility model. As CGS increased, the effects of negative maternal parenting on mother-son conflict were magnified. These findings have implications for the timing and focus of interventions aimed at improving parent-adolescent relationships. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation. Methods: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C0) were collected for 3 intervals: 0–3 months, 3–12 months, and 12–24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C0 and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality. Results: The influence of CYP3A5*3 polymorphism was only significant for C0 and IPV during the first 3 months. Low C0 (< 8 ng/mL) at 3–12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046–6.953) and mortality (HR 2.531, 95% CI 1.368–4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336–4.839). Patients with Low C0/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279–15.008) and survival (HR 6.179, 95% CI 2.598–14.698), surpassing the predictive power provided by C0 or IPV alone. Conclusion: A combination of Low C0/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation. [ABSTRACT FROM AUTHOR]

Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), and is mainly metabolized by CYP2D6, CYP3A4, and flavin‐containing monooxygenase 1. The purpose of the study was to evaluate the effect of CYP2D6 polymorphism on the pharmacokinetics of dapoxetine in healthy Chinese men. Thirty‐nine subjects who received a single oral dose of 30 mg dapoxetine hydrochloride were classified based on their CYP2D6 genotype: *1/*1 (n = 9), *1/*41 (n = 1), *1/*10 (n = 12), *10/*41 (n = 3), or *10/*10 (n = 14). The difference in pharmacokinetic parameters between different genotype groups was analyzed and then scored according to the activity score system. Compared with the wild‐type subjects of CYP2D6 *1/*1, the peak plasma concentration (Cmax) and the area under the plasma drug concentration‐time curve (AUCinf) of dapoxetine in the *10/*10 and *10/*41 groups were notably increased (P ≤.05). Significant differences in Cmax, AUC, volume of distribution/bioavailability (V/F) and clearance/bioavailability (CL/F) were observed among dapoxetine activity score groups (P ≤.05). The AUCinf was increased significantly (154% and 89.73%, P ≤.05) and the Cmax was increased significantly (73.45% and 42.67%, P ≤.05) in CYP2D6 *10/*41 subjects, compared with CYP2D6 *1/*1 and *1/*10 subjects. The results obtained indicated that CYP2D6 *10 and *41 polymorphisms have significant effects on the pharmacokinetic properties of dapoxetine. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate for associations of polymorphisms for potassium channel genes in patients with breast cancer who were classified as having high or low-moderate levels of cancer-related cognitive impairment (CRCI). SAMPLE & SETTING: 397 women who were scheduled to undergo surgery for breast cancer on one breast were recruited from breast care centers located in a comprehensive cancer center, two public hospitals, and four community practices. METHODS & VARIABLES: CRCI was assessed using the Attentional Function Index prior to and for six months after surgery. The attentional function classes were identified using growth mixture modeling. RESULTS: Differences between patients in the high versus low-moderate attentional function classes were evaluated. Six single nucleotide polymorphisms for potassium channel genes were associated with low-moderate class membership. IMPLICATIONS FOR NURSING: The results contribute to knowledge of the mechanisms for CRCI. These findings may lead to the identification of high-risk patients and the development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Objective: Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and cerebral venous sinus thrombosis (CVST). We report the role of cytochrome P450 (CYP2C9*2/*3) and vitamin K epoxide reductase subunit 1 (VKORC1) genotypes and acquired causes in maintaining stability of anticoagulation following acenocoumarin in cardioembolic stroke and CVST. Methods: The study comprised 157 individuals with cardioembolic stroke and CVST who were on acenocoumarin. Their comorbidities, comedication, and dietary habits were noted. Prothrombin time and international normalized ratio (INR) were measured during follow-up, and the coagulation status was categorized as stable (>50% occasions in therapeutic range) and unstable (>50% below and above therapeutic range). Genotyping of VKORC1, CYP2C9*2, and CYP2C9*3 was done by polymerase chain reaction-restriction fragment length polymorphism. Bleeding and embolic complications were noted. The predictors of unstable INR were evaluated using multivariate analysis. Results: INR was stable in 47.8% and unstable in 52.2% of patients. Patients with mutant genotypes required low dose of acenocoumarin. The predictors of unstable INR were metallic valve (odds ratio [OR] 4.07, 95% confidence interval [CI] 1.23-13.49, P = 0.02), use of digoxin (OR 0.031, 95% CI 0.13-0.74, P = 0.09), proton pump inhibitor (OR 0.23, 95% CI 0.06-0.91, P = 0.037), sodium valproate (OR 0.22, 95% CI 0.05-0.85, P = 0.029), and CYP2C9*2 genotype (OR 5.57, 95% CI 1.19-26.06, P = 0.02). Conclusions: Variant genotypes of VKORC1, CYP2C9*2, and CYP2C9*3 required lower dose of acenocoumarin, and CYP2C9*2 was associated with unstable INR. Comedication is a modifiable risk factor that needs attention. [ABSTRACT FROM AUTHOR]

Background: The FTO gene polymorphisms may influence the effects of lifestyle interventions on obesity. The present study aimed to assess the influence of the rs9930506 FTO gene polymorphism on the success of a comprehensive weight loss intervention in male adolescents with overweight and obesity. Methods: This study was carried out on 96 adolescent boys with overweight and obesity who were randomly assigned to the intervention (n = 53) and control (n = 43) groups. The blood samples of the participants were collected, and the FTO gene was genotyped for the rs9930506 polymorphism. A comprehensive lifestyle intervention including changes in diet and physical activity was performed for 8 weeks in the intervention group. Results: Following the lifestyle intervention, BMI and fat mass decreased significantly in the intervention group compared with the control group (both p < 0.05), while no change was found in weight, height or body muscle percentage between the groups. The participants in the intervention group with the AA/AG genotype and not in carriers of the GG genotype had a significantly higher reduction in BMI (−1.21 vs. 1.87 kg/m2, F = 4.07, p < 0.05) compared with the control group. Conclusion: The intervention in individuals with the AA/AG genotype has been significantly effective in weight loss compared with the control group. The intervention had no association effect on anthropometric indices in adolescents with the GG genotype of the FTO rs9930506 polymorphism. Trial Registration: Name of the registry: National Nutrition and Food Technology Research Institute; Trial registration number: IRCT2016020925699N2; Date of registration: 24/04/2016; URL of trial registry record: https://www.irct.ir/trial/21447 [ABSTRACT FROM AUTHOR]

Background: Molar hypomineralization (MH) is defined as a multifactorial condition, and thus, its presence may be defined by interactions between environmental and genetic factors. Aim: To evaluate the association between MH, genes involved in enamel development, and the use of medication during pregnancy in early childhood. Design: One hundred and eighteen children, 54 with and 64 without MH, were studied. The data collected included demographics, socioeconomic data, and the medical history of mothers and children. Genomic DNA was collected from saliva. Genetic polymorphisms in ameloblastin (AMBN; rs4694075), enamelin (ENAM; rs3796704, rs7664896), and kallikrein (KLK4; rs2235091) were evaluated. These genes were analyzed by real‐time polymerase chain reaction using TaqMan chemistry. The software PLINK was used to compare allele and genotype distributions of the groups and to assess the interaction between environmental variables and genotypes (p <.05). Results: The variant allele KLK4 rs2235091 was associated with MH in some children (odds ratio [OR]: 3.75; 95% confidence interval [CI] = 1.65–7.81; p =.001). Taking medications in the first 4 years of life was also associated with MH (OR: 2.94; 95% CI = 1.02–6.04; p =.041) and specifically in association with polymorphisms in ENAM, AMBN, and KLK4 (p <.05). The use of medications during pregnancy was not associated with MH (OR: 1.37; 95% CI = 0.593–3.18; p =.458). Conclusion: The results of this study suggest that taking medication in the postnatal period appears to contribute to the etiology of MH in some evaluated children. There may be a possible genetic influence of polymorphisms in the KLK4 gene with this condition. [ABSTRACT FROM AUTHOR]

Background: Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters. Methods: This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method. Results: There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53–5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6–1510) ng/ml compared to controls, median (IQR) of 1675 (536.8–2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005). Conclusions: Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production. [ABSTRACT FROM AUTHOR]

Background. There is no conclusive evidence on the association between interleukin- (IL-) 6 gene polymorphism and type 2 diabetes mellitus (type 2 DM). Thus, this study is aimed at evaluating the role of rs1800795 and rs1800796 polymorphisms in the pathogenesis of type 2 DM among Ghanaians in the Ho Municipality. Materials and Methods. We recruited into this hospital-based case-control study 174 patients with type 2 DM (75 DM alone and 99 with DM+HTN) and 149 healthy individuals between 2018 and 2020. Demographic, lifestyle, clinical, anthropometric, and haemodynamic variables were obtained. Fasting blood samples were collected for haematological, biochemical, and molecular analyses. Genomic DNA was extracted, amplified using Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique, and genotyped for IL-6 gene polymorphism. Logistic regression analyses were performed to assess the association between IL-6 gene polymorphism and type 2 DM. Results. The minor allele frequency (MAF) of the rs1800795 and rs1800796 polymorphisms was higher in DM alone (57.5%, 62.0%) and DM with HTN groups (58.3%, 65.3%) than controls (33.1%, 20.0%). Carriers of the rs1800795GC genotype (aOR = 2.35 , 95% CI: 1.13-4.90, p = 0.022) and mutant C allele (aOR = 2.41 , 95% CI: 1.16-5.00, p = 0.019) as well as those who carried the rs1800796GC (aOR = 8.67 , 95% CI: 4.00-18.90, p < 0.001) and mutant C allele (aOR = 8.84 , 95% CI: 4.06-19.26, p = 0.001) had increased odds of type 2 DM. For both polymorphisms, carriers of the GC genotype had comparable levels of insulin, HOMA-IR, and fasting blood glucose (FBG) with those who carried the GG genotype. IL-6 levels were higher among carriers of the rs1800796GC variant compared to carriers of the rs1800796GG variant (p = 0.023). The rs1800796 polymorphism, dietary sugar intake, and exercise status, respectively, explained approximately 3% (p = 0.046), 3.2% (p = 0.038 , coefficient = 1.456), and 6.2% (p = 0.004 , coefficient = − 2.754) of the variability in IL-6 levels, suggesting weak effect sizes. Conclusion. The GC genotype and mutant C allele are risk genetic variants associated with type 2 DM in the Ghanaian population. The rs1800796 GC variant, dietary sugar intake, and exercise status appear to contribute significantly to the variations in circulating IL-6 levels but with weak effect sizes. [ABSTRACT FROM AUTHOR]

Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by binding to vitamin D receptor (VDR). Associations between VDR gene polymorphism and Alzheimer's disease (AD), Parkinson's disease (PD), and mild cognitive impairment (MCI) risk has been investigated extensively, but the results remain ambiguous. The aim of this study was to comprehensively assess the correlations between four VDR polymorphisms (FokI, BsmI, TaqI, and ApaI) and susceptibility to AD, PD, and MCI. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the relationship of interest. Pooled analyses suggested that the ApaI polymorphism decreased the overall AD risk, and the TaqI increased the overall PD susceptibility. In addition, the BsmI and ApaI polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the TaqI and ApaI genotypes reduced the AD predisposition among Caucasians, while the TaqI polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the ApaI variant elevated the predisposition to MCI in Caucasians and Asians. Further studies are need to identify the role of VDR polymorphisms in AD, PD, and MCI susceptibility. [ABSTRACT FROM AUTHOR]

Purpose. Recurrent miscarriage (RM) is a significant reproductive concern affecting numerous women globally. Genetic factors are believed to play a crucial role in RM, making the histidine-rich glycoprotein (HRG) gene, a topic of interest due to its potential involvement in angiogenesis. This study is aimed at investigating the association between the HRG rs10770 genotype and RM. Method. Blood samples were collected from a total of 200 women at the beginning of the study. Subsequently, a comparative analysis was conducted between the blood samples of 100 women with a history of RM (case group) and the blood samples of another 100 healthy women (control group). HRG rs10770 genotyping was performed through polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP), followed by statistical analysis to evaluate the relationship between HRG rs10770 genotype and RM. Results. The results indicated a significant statistical difference between the C/C genotype (OR = 3.32 , CI: 1.22-9.04, p = 0.01) and the C/T genotype (OR = 1.24 , CI: 0.67-2.30, p = 0.47) in both the case and control groups. Additionally, a significant correlation was observed in the C allelic frequency among RM participants compared to the control group (OR = 1.65 , CI: 1.06-2.58, p = 0.02). Conclusion. The study highlights the importance of HRG rs10770 in understanding RM, shedding light on its implications for reproductive health. Furthermore, it became evident that women carrying the homozygous C/C genotype exhibited increased susceptibility to the risk of RM. [ABSTRACT FROM AUTHOR]