Association Of Single Nucleotide Polymorphisms Research Articles

The association of the prothrombin A19911G single-nucleotide polymorphism and the risk of venous thromboembolism: A systematic review and meta-analysis.

The study employed meta-analysis to provide a comprehensive synthesis of evidence regarding the association between the prothrombin A19911G polymorphism and the risk of venous thromboembolism (VTE). The databases were searched to identify studies investigating the association between the prothrombin A19911G polymorphism and the risk of VTE. Meta-analysis was conducted using Stata 14.0 software. A total of five literature studies were included, involving 14,001 participants. Meta-analysis demonstrated that prothrombin A19911G polymorphism increased the risk of VTE (G vs A: OR = 1.17, 95% CI = 1.11-1.22, p < .00001; GG + AG vs AA: OR = 1.22, 95% CI = 1.13-1.31, p < .00001; GG vs AG + AA: OR = 1.23, 95% CI = 1.14-1.33, p < .00001; AG vs AA: OR = 1.15, 95% CI = 1.06-1.25, p = .0006; GG vs AA: OR = 1.34, 95% CI = 1.22-1.48, p < .00001). The polymorphism of prothrombin A19911G enhances the susceptibility to VTE.

The deficiency of DNASE1L3 does not affect systemic sclerosis pathogenesis in two inducible murine models of the disease.

We induced systemic sclerosis (SSc)-like disease in both wild-type and Dnase1l3-deficient mice using two distinct approaches involving bleomycin and hypochlorous acid injections. Our observations revealed that the deficiency in DNASE1L3 did not affect tissue fibrosis or inflammation caused by these treatments. Despite the association of single nucleotide polymorphisms in humans with SSc pathogenesis, our study demonstrates that DNASE1L3 is dispensable in two inducible murine models of SSc-like pathogenesis.

Association of single nucleotide polymorphism at BMP2 gene with iron deficiency status among anaemic patients in Hospital Universiti Sains Malaysia

BackgroundIron deficiency contributes for over half of all anaemia cases, especially among women and children. Iron deficiency anaemia remains a serious public health concern worldwide. The aim of this study is to determine the association between the single nucleotide polymorphism rs235756 in the bone morphogenetic protein 2 (BMP2) gene and iron deficiency status.Results104 total anaemic samples were selected from Hospital Universiti Sains Malaysia. ARMS-PCR was performed to genotype the rs235756 SNP in the 104 samples. The genotype distribution of BMP2 rs235756 showed that AG genotypes had the highest frequency 51(86.4%) followed by GG 6(10.2%) and AA 2(3.4%) in IDA group, whereas AG 42(93.3%), AA 2(4.4%) and GG 1(2.2%) were found in the other anaemia group. The minor allele frequency in BMP 2 rs235756 from this study (0.514) was not similar to the East Asian (EAS) population (0.135); however, the allelic frequency showed significant association between these two. The mean of total iron binding capacity level differed significantly between homozygous-dominant AA and AG + GG genotypes (P < 0.05) but no significant difference for the mean of haematological parameter, ferritin and serum iron.ConclusionsIn future clinical settings, this finding can potentially be as a guide in the early prediction for IDA patients through the genetic testing.

Association of HLA-E single nucleotide polymorphisms with human myeloid leukemia.

Single nucleotide polymorphisms (SNPs) of HLA-E are related to the occurrence of many diseases, but their functions remain unclear. In this study, the function of SNPs at HLA-E rs76971248 and rs1264457 on the myeloid leukemia cells was analyzed by a progressive procedure, included genotyping, mRNA transcription, regulatory element, protein expression, and anti-tumor effect. The frequencies of rs76971248 G and rs1264457 G were found higher in myeloid leukemia patients than those in healthy blood donors (p < 0.05). For myeloid leukemia, rs76971248 T was protective, while rs1264457 G was susceptible. We also found that rs76971248 affected HLA-E mRNA transcription and membrane HLA-E (mHLA-E) expression in K562 cells through differently binding to transcription factor HOXA5 (p < 0.0001), while rs1264457 affected mHLA-E expression by changing mRNA transcription and an encoding amino acid (p < 0.01). In contrast, the expression of soluble HLA-E (sHLA-E) was not influenced by both rs1264457 and rs76971248. The higher HLA-E expression was detected among myeloid leukemia patients, and the K562 cells with higher HLA-E molecules played a significant inhibitory effect on the killing activity of NK-92MI cells (p < 0.05). In conclusion, the higher HLA-E expression of myeloid leukemia cells is promoted by rs76971248 G and rs1264457 G, which helps escape from NK-92MI cells' killing.

Utilising SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is a prevalent, multifactorial form of hair loss involving complex aetiological factors, such as altered androgen regulation and energy metabolism. Existing treatments offer limited success, thus highlighting the need for advanced, personalised therapeutic strategies. This study focuses on correlating the genetic mechanisms of AGA with molecular targets involved in the response to current treatment modalities. An anonymised database including 26,607 patients was subjected to analysis. The dataset included information on patients' genotypes in 26 single nucleotide polymorphisms (SNPs), specifically, and diagnosed AGA grades, representing a broad range of ethnic backgrounds. In our sample, 64.6% of males and 35.4% of females were diagnosed with female pattern hair loss. This distribution aligns well with prior studies, thus validating the representativeness of our dataset. AGA grading was classified using the Hamilton-Norwood and Ludwig scales, although no association was found to the grade of the disease. SNP association analysis revealed eight SNPs, namely rs13283456 (PTGES2), rs523349 (SRD5A2), rs1800012 (COL1A1), rs4343 (ACE), rs10782665 (PTGFR), rs533116 (PTGDR2), rs12724719 (CRABP2) and rs545659 (PTGDR2), to be statistically significant with a p-value below 0.05. The study establishes a preliminary association between eight specific SNPs and AGA. These genetic markers offer insights into the variability of therapeutic responses, thus underlining the importance of personalised treatment approaches. Our findings show the potential for more targeted research to understand these SNPs' and further roles in AGA pathophysiology and in modulating treatment response.

Haplotype of \(\textit{TEX15}\) single nucleotide variants associated with male infertility in 401 Vietnamese individuals

Spermatogenesis is a process of cell differentiation to produce fertilized sperm. Testis-expressed 15 (TEX15), an important gene in spermatogenesis, has been reported to be linked with male infertility in various populations. This study aimed to assess the association of single nucleotide polymorphism (SNP) TEX15 rs323347 with male infertile individuals in a Vietnamese cohort and further analyze the haplotypes of TEX15 rs323346 and TEX15 rs323347. A total of 401 unrelated males, including 202 male infertility patients and 199 healthy controls were genotyped for TEX15 rs323347 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Using statistical methods, the results showed that the allele frequencies of TEX15 rs323347 were in agreement with Hardy-Weinberg equilibrium (HWE) (p-value &gt; 0.05), but its genotype frequencies were not significantly different between male infertility patient and control groups (p-values &gt; 0.05). However, the CA haplotype of the two variants (rs323346 and rs323347) increased the risk of male infertility (p = 0.046, OR = 2.547, 95% CI = 0.982–6.602). Thus, this study would enrich the knowledge of the impact of genetic factors on male infertility in the Vietnamese population.

Role of ABCA1 in Atherosclerosis: Novel Mutations and Potential Plant-derived Therapies.

ATP-binding cassette transporter A1 (ABCA1) is one of the key proteins regulating cholesterol homeostasis and playing a crucial role in atherosclerosis development. ABCA1 regulates the rate-limiting step of reverse cholesterol transport, facilitates the efflux of surplus intracellular cholesterol and phospholipids, and suppresses inflammation through several signalling pathways. At the same time, many mutations and Single Nucleotide Polymorphisms (SNPs) have been identified in the ABCA1 gene, which affects its biological function and is associated with several hereditary diseases (such as familial hypo-alpha-lipoproteinaemia and Tangier disease) and increased risk of cardiovascular diseases (CVDs). This review summarises recently identified mutations and SNPs in their connection to atherosclerosis and associated CVDs. Also, we discuss the recently described application of various plant-derived compounds to modulate ABCA1 expression in different in vitro and in vivo models. Herein, we present a comprehensive overview of the association of ABCA1 mutations and SNPs with CVDs and as a pharmacological target for different natural-derived compounds and highlight the potential application of these phytochemicals for treating atherosclerosis through modulation of ABCA1 expression.

Association of single nucleotide polymorphisms in ITLN1 gene with ischemic stroke risk in Xi'an population, Shaanxi province.

Ischemic stroke (IS) is the main cause of death and adult disability. However, the pathogenesis of this complicated disease is unknown. The present study aimed to assess the relationship between ITLN1 single nucleotide polymorphisms (SNPs) and the susceptibility to IS in Xi'an population, Shaanxi province. In this study, we designed polymerase chain reaction (PCR) primers located at -3,308 bp upstream of the transcription initiation site within promoter region of the ITLN1 gene. The target fragment was amplified by PCR and identified by agarose gel electrophoresis. Sanger sequencing was then performed in the samples extracted from a cohort comprising 1,272 participants (636 controls and 636 cases), and the obtained sequences were compared with the reference sequences available on the National Center for Biotechnology Information (NCBI) website to detect SNPs in the ITLN1 gene promoter region. Logistic regression analysis was employed to assess the relationship between ITLN1 polymorphisms and IS risk, with adjustments for age and gender. Significant positive results were tested by false-positive report probability (FPRP) and false discovery rate (FDR). The interaction among noteworthy SNPs and their predictive relationship with IS risk were explored using the Multi-Factor Dimensionality Reduction (MDR) software. The results of Sanger sequencing were compared with the reference sequences on the NCBI website, and we found 14 SNPs in ITLN1 gene promoter satisfied Hardy-Weinberg equilibrium (HWE). Logistic regression analysis showed that ITLN1 was associated with a decreased risk of IS (rs6427553: Homozygous C/C: adjusted OR: 0.69, 95% CI [0.48-0.97]; Log-additive: adjusted OR: 0.83, 95% CI [0.70-0.98]; rs7411035: Homozygous G/G: adjusted OR: 0.66, 95% CI [0.47-0.94]; Dominant G/T-G/G: adjusted OR: 0.78, 95% CI [0.62-0.98]; Log-additive: adjusted OR: 0.81, 95% CI [0.69-0.96]; rs4656958: Heterozygous G/A: adjusted OR: 0.74, 95% CI [0.59-0.94]; Homozygous A/A: adjusted OR: 0.51, 95% CI [0.31-0.84]; Dominant G/A-A/A: adjusted OR: 0.71, 95% CI [0.57-0.89]; Recessive A/A: adjusted OR: 0.59, 95% CI [0.36-0.96]; Log-additive: adjusted OR: 0.73, 95% CI [0.61-0.88]), especially in people aged less than 60 years and males. In short, our study revealed a correlation between ITLN1 variants (rs6427553, rs7411035 and rs4656958) and IS risk in Xi'an population, Shaanxi province, laying a foundation for ITLN1 gene as a potential biomarker for predicting susceptibility to IS.

Abstract 6103: The association of genetic polymorphisms in DNA repair genes XRCC1 and 3 with cervical cancer risk among Bangladeshi females

Abstract Introduction and Objective: Worldwide, cervical cancer ranks the second most common cancer in women. Sequence variations in DNA repair genes X-ray repair cross complementing (XRCC) 1 and 3 genes can lead to can result cellular function aberration leading to cancers. Single nucleotide polymorphisms (SNPs) in XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) genes have been shown to cause individual variation in their DNA repair capacity. The aim of this study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met SNPs with susceptibility to cervical cancer among Bangladeshi populations. Methods: In the current case-control study 124 cervical cancer patients and 148 age matched healthy controls were recruited. Genomic DNAs were isolated from peripheral blood collected from the participants and genotyped for candidate SNPs using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: For XRCC1, heterozygous Arg/Gln and combined heterozygous plus variant homozygous Gln/Gln genotypes showed 1.78-fold (95% CI 1.0037 to 2.8771, p=0.0484) and 1.8627-fold (95% CI 1.1470 to 3.0250, p = 0.0119) increased risk of cervical cancer, respectively, when compared with normal homozygous Arg/Arg genotype. The variant Gln allele was positively associated with cervical cancer by 1.68-fold increase (95% CI 1.1732 to 2.3980, p = 0.0046). Similarly, for XRCC3, Thr/Met heterozygous and combined Thr/Met + Met/Met genotypes were found to be associated with 1.6993-fold (95% CI 1.0398 to 3.0166, p=0.0354) and 1.8312-fold (95% CI 1.0890 to 3.0791, p = 0.0225) higher risk, respectively, when compared with normal homozygous Thr/Thr genotypes. The variant Met allele showed significant association with 1.71-fold increased risk. Conclusion: XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) SNPs may be positively associated with increased cervical cancer risk in Bangladeshi females. Citation Format: Md Mustafizur Rahman, Laboni Das, Sadia Rahman, Amir Hossain, Razia Sultana. The association of genetic polymorphisms in DNA repair genes XRCC1 and 3 with cervical cancer risk among Bangladeshi females [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6103.

Abstract 6130: Association of vitamin D-related genetic variants and prostate cancer risk in Black men

Abstract Background: What we know of the relationship between vitamin D status and prostate cancer has largely been characterized among men of European ancestry, hereafter referred to as “White”. Research among White men indicate positive associations between circulating vitamin D status, as measured by concentrations of 25-hydroxyvitamin D (25(OH)D), with prostate cancer risk, and that genetic scores based on genome-wide associated single nucleotide polymorphisms (SNPs) reflecting high vs. low 25(OHD) is positively associated with aggressive disease. Limited research exists elucidating this relationship among men of African ancestry, hereafter referred to as “Black”. This is despite the fact that Black populations experience chronically lower circulating 25(OH)D, and ancestry-specific differences in genetic variants in some vitamin D-related genes. Given the paucity of research in this area, we examined the role of genetic variants in six commonly studied genes in the vitamin D pathway involved in synthesis (CYP27A1 and CYP27B1), transport (GC), activity (VDR and RXR), and metabolism (CYP24A1) in relation to prostate cancer among Black men. Methods: We assessed a total of 78 candidate SNPs in six vitamin D pathway genes that were either previously associated with circulating 25(OHD) and/or associated with prostate cancer risk in studies of White men. We compared vitamin D gene SNP associations with prostate cancer in Black and White men using summary statistics from a large GWAS of over 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men. A statistical significance threshold of 0.00064 (0.05/78 candidate SNPs) was used to adjust for multiple comparisons. Results: None of the examined SNPs were significantly associated with prostate cancer risk among Black men after adjustment for multiple comparisons. However, four SNPs were nominally significant in Black men, including two in RXR [rs41400444 OR=1.09, 95% CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.867-0.999, P = 0.04556] and two in VDR [rs2853563 OR = 1.07, 1.012-1.13, P = 0.0173 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.0495]. The latter SNP rs1156882 was also positively associated with prostate cancer risk in White men (OR = 1.035, 1.02-1.06, P = 0.00024), along with VDR SNP rs4516035 (OR = 1.027, 1.012-1.042, P = 0.00055), both after correction for multiple comparisons. Conclusions: We observed non-significant, though suggestive, associations between genetic variants in vitamin D pathway genes previously associated with prostate cancer or vitamin D levels in White populations and prostate cancer risk in Black men. Future research exploring the potential role of vitamin D pathway genes and prostate cancer in Black men – a population at high risk both for low circulating vitamin D and prostate cancer - will need to identify vitamin D-related genetic variants specific to carcinogenesis in Black men. Citation Format: Tracy M. Layne, Joseph H. Rothstein, Xiaoyu Song, Weiva Sieh, Robert J. Klein. Association of vitamin D-related genetic variants and prostate cancer risk in Black men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6130.

Gene polymorphisms of molecules of the cGAS-STING signalling pathway are associated with AML in Chinese patients

PurposeThe aim of this study was to explore the relationships between single-nucleotide polymorphisms (SNPs) of crucial molecules in the cGAS-STING signalling pathway and the susceptibility to, induction chemotherapy response of, and prognosis of acute myeloid leukaemia (AML) in Chinese patients.MethodsThirteen SNPs of crucial molecules in the cGAS-STING signalling pathway were genotyped in 262 AML patients using the Sequenom MassARRAY system. The associations of SNPs with susceptibility, and induction chemotherapy response were analysed using the chi-square test or Fisher’s exact test and univariate binary logistic regression, the connection of SNPs with prognosis of AML was analysed using the log-rank test, and Kaplan–Meier curves were applied for survival estimation.ResultsIn our study, gene polymorphisms of cGAS-STING signalling pathway molecules could be vitally associated with AML. In the recessive model, the cGAS rs311678 gene polymorphism could be closely related to AML susceptibility (CC vs. TT + TC, odds ratio (OR) = 0.480, 95% confidence interval (CI) = 0.260–0.889, p = 0.020). Moreover, IKKA rs3808917 might be associated with the WBC count, cGAS rs311678 could be associated with the bone marrow (BM) blast percentage, and NF-κB rs1056890 under codominant and recessive models could be connected with the HGB level. Patients who were STING rs7380272 TT/CT carriers was likely to have higher insensitivity to induction chemotherapy than CC carriers (TT + CT vs. CC, OR = 2.917, 95% CI = 1.073–7.929, p = 0.036). Survival analysis indicated that the IKKB rs3747811 TT genotype might be associated with decreased overall survival (OS) (p < 0.05).ConclusionsSNPs of molecules in the cGAS-STING signalling pathway could be significantly associated with AML. The cGAS rs311678 gene polymorphism could be associated with AML susceptibility, the STING rs7380272 variant might be related to induction chemotherapy response, and IKKB rs3747811 tended to be associated with AML overall survival. Moreover, IKKA rs3808917 could be associated with the WBC count, cGAS rs311678 could be associated with the BM blast percentage, and NF-κB rs1056890 might be related to the HGB level.

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses

Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations.

The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus (T2DM) is currently controversial. It is unknown whether this association can be gene realized across different populations. To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM. We searched PubMed, Embase, Web of Science, Cochrane Library, Medline, Baidu Academic, China National Knowledge Infrastructure, China Biomedical Liter-ature Database, and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12, 2022. Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature. Twelve case-control studies (including 11273 cases and 11654 controls) met our inclusion criteria. In the full population, allelic model [odds ratio (OR): 1.19; 95% confidence interval (95%CI): 1.09-1.29; P < 0.0001], recessive model (OR: 1.20; 95%CI: 1.11-1.29; P < 0.0001), dominant model (OR: 1.27. 95%CI: 1.14-1.42; P < 0.0001), and codominant model (OR: 1.36; 95%CI: 1.15-1.60; P = 0.0003) (OR: 1.22; 95%CI: 1.10-1.36; P = 0.0002) indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM. In stratified analysis, this association was confirmed in Asian populations: allelic model (OR: 1.25; 95%CI: 1.13-1.37; P < 0.0001), recessive model (OR: 1.29; 95%CI: 1.11-1.49; P = 0.0007), dominant model (OR: 1.35; 95%CI: 1.20-1.52; P < 0.0001), codominant model (OR: 1.49; 95%CI: 1.22-1.81; P < 0.0001) (OR: 1.26; 95%CI: 1.16-1.36; P < 0.0001). In non-Asian populations, this association was not significant: Allelic model (OR: 1.06, 95%CI: 0.98-1.14; P = 0.12), recessive model (OR: 1.04; 95%CI: 0.75-1.42; P = 0.83), dominant model (OR: 1.06; 95%CI: 0.98-1.15; P = 0.15), codominant model (OR: 1.08; 95%CI: 0.82-1.42; P = 0.60. OR: 1.15; 95%CI: 0.95-1.39; P = 0.14). KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population. Carriers of the C allele had a higher risk of T2DM. This association was not significant in non-Asian populations.

Rs4862705 in the melatonin receptor 1A gene is associated with renal function decline in type 1 diabetes individuals.

The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (MTNR1A). Eight SNPs in MTNR1A were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated. The group of individuals with a renal function decline ≥ 5 mL min-1 1.73 m-2 year-1 presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; p = 0.0046). No other significant associations were found. This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.

Genetic Variations in Susceptibility to Traumatic Muscle Injuries and Muscle Pain among Brazilian High-Performance Athletes.

Traumatic muscle injuries (TMIs) and muscle pain (MP) negatively impact athletes' performance and quality of life. Both conditions have a complex pathophysiology involving the interplay between genetic and environmental factors. Yet, the existing data are scarce and controversial. To provide more insights, this study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) previously linked to athletic status with TMI and MP after exercise among Brazilian high-performance athletes from different sports modalities (N = 345). The impact of important environmental determinants was also assessed. From the six evaluated SNPs (ACTN3 rs1815739, FAAH rs324420, PPARGC1A rs8192678, ADRB2 rs1042713, NOS3 rs1799983, and VDR rs731236), none was significantly associated with TMI. Regarding MP after exercise, ACTN3 rs1815739 (CC/CT vs. TT; adjusted odds ratio (aOR) = 1.90; 95% confidence interval (95%Cl), 1.01-3.57) and FAAH rs324420 (AA vs. AC/CC; aOR = 2.30; 95%Cl, 1.08-4.91) were independent predictors according to multivariate binomial analyses adjusted for age (≥23 vs. <23 years), sex (male vs. female), and tobacco consumption (yes vs. no). External validation is warranted to assess the predictive value of ACTN3 rs1815739 and FAAH rs324420. This could have implications for prophylactic interventions to improve athletes' quality of life.

Genetic Background of Acute Heart Rate Response to Exercise.

The acute heart rate response (AHRR) to physical activity, which refers to the change in heart rate during and after exercise, has been associated with cardiovascular and all-cause mortality. Previous studies have shown that AHRR is significantly determined by genetics in addition to environmental and lifestyle factors. The aim of this study was to investigate the genetic background of AHRR by analysing ten single nucleotide polymorphisms (SNPs) associated with leisure-time physical activity (LTPA) in 620 samples from the Hungarian population. The AHRR can be characterised as the difference between post-exercise and resting heart rate, i.e., the delta heart rate (ΔHR) defined by the YMCA 3 min step test, with a lower value indicating better cardiovascular fitness. The association of SNPs with ΔHR was analysed both separately and in combination using an optimised polygenic score (oPGS). The results showed that five SNPs (rs10252228, rs459465, rs6022999, rs8097348, and rs12405556) had at least nominally significant (p < 0.05) individual associations with ΔHR. After optimizing the PGS, a cumulative effect was observed for eight SNPs (rs6022999, rs12405556, rs459465, rs10252228, rs8097348, rs10887741, rs12612420, and rs7023003) that had a strong and statistically significant association with ΔHR (B = -2.51, 95% CI: -3.46--1.76; p = 2.99 × 10-9). Of the four main domains of physical activity, the oPGS showed a significant positive association only with LTPA (B = 84.60; 95%CI: 25.23-143.98; p = 0.005). In conclusion, our results suggest that the SNPs we investigated influence individual leisure-time physical activity, mediated by their effects on the acute heart rate response.

Association of long noncoding RNA H19 rs2839698 C/T with hepatitis B virus infection and hepatocellular carcinoma risk.

The intricate pathogenesis of the hepatitis B virus (HBV) and its progression to hepatocellular carcinoma (HCC) have not yet been fully elucidated. H19 is one of the earliest imprinted long noncoding RNAs (lncRNAs) associated with liver pathobiology. This study investigated the association of H19 single nucleotide polymorphisms (SNPs) rs2839698 C/T and rs217727 C/T with HBV and HBV-related HCC and their correlation with H19 expression level. A total of 230 subjects were enrolled in this study including 100 HBV-infected patients, 30 HBV-related HCC patients, and 100 apparently healthy controls. TaqMan genotyping human assays were utilized to assess allelic discrimination for H19 SNPs. H19 expression was assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Our findings showed that H19 rs2839698 was linked to a higher incidence of HBV infection and HBV-related HCC. Individuals who bear the CT genotype of rs2839698 were more susceptible to HBV infection (OR = 3.05; 95% CI 1.714-5.457; p < 0.001). Those harboring the TT genotype were more prone to develop HCC (OR = 2.625; 95% CI 1.037-6.64; p = 0.038). Our data revealed that rs2839698 could function as a promising predictor of HCC risk. Furthermore, H19 was significantly downregulated in HBV (p < 0.01) and HCC (p < 0.01) patients versus the control group. Significant upregulation of H19 in HCC patients with cirrhosis (p < 0.001) was detected. Altogether, this is considered the first prospective case-control study to address the implication of the genetic variations of H19 SNPs in HBV and HBV-related HCC in Egyptian patients.

Adiponectin Gene Polymorphisms: A Case-Control Study on Their Role in Late-Onset Alzheimer's Disease Risk.

Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5' region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.

SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese

BackgroundDrug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese.MethodsA total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping.ResultsBoth single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction.ConclusionsThese findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

(249) Association of Single Nucleotide Polymorphisms (rs2301365 &amp; Rs737008) in PRM1 Gene and Male Infertility: A Meta-Analysis

Abstract Introduction In the sperm nucleus, protamine is a major DNA-binding protein that replaces histone. It is a basic arginine-rich protein responsible for DNA compaction. Protamin I (PRM1) is one of the important genes that produces protamine. Mutations and polymorphisms in PRM1 may increase the odds of male infertility. Objective The present meta-analysis investigated the association of single nucleotide polymorphisms (SNPs) (rs2301365 &amp; rs737008) in the PRM1 gene and male infertility. Methods The original research articles, published till July 2023 in the English language, on the association of rs2301365 and rs737008 in the PRM1 gene and male infertility, were retrieved from Science Direct, PubMed, NCBI and Google Scholar. Results A total of 129 studies were retrieved by searching in the different databases, after the removal of duplicates, meta-analysis, and abstracts, 14 were finally selected. In 11 case-control studies, the association of the rs2301365 (-190C &amp;gt;A) polymorphism was presented as the meta-analysis of different models, Allelic model (C vs. A), Dominant model (CC + CA vs. AA), Recessive model (CC vs. CA + AA), Additive model (CC vs. AA), Heterozygous model (AC vs. AA). Allelic, additive, dominant and heterozygous models reported that the -190C&amp;gt;A (rs2301365) increased the odds of male infertility. The ethnic subgroup analysis showed the same pattern of association for the Caucasian infertile men. However, none of these overall and subgroup analyses based on ethnicity showed an association between rs2301365 (-190C &amp;gt;A) and infertility in Asian men. For rs737008 (139C &amp;gt; A) in the meta-analysis of 14 studies, none of these overall and subgroup analyses based on ethnicity showed an association with male infertility. Trial sequential analysis (TSA) for the allelic model of rs2301365 (-190C &amp;gt;A) showed the required sample size was 2252 at 90% power and 5% type-I error, whereas the cumulative z-curve crossed the trial sequential monitoring boundaries of harm. However, the sample size was greater than required therefore further studies will not likely change results. For rs737008 (139C &amp;gt; A), TSA recommended more studies to be conducted. Conclusions The PRM1 rs2301365 (-190C &amp;gt;A) was associated with male infertility in overall analysis and Caucasian men. Further studies on this SNP may not change results. However, rs737008 (139C &amp;gt; A) was not associated with male infertility. However, further studies are recommended. Disclosure No.