Association Of Variants Research Articles

Genetic factors related to aspirin resistance using the Multiplate® device in Hong Kong Chinese patients with stable coronary heart disease

ObjectiveAssociations between single nucleotide polymorphisms (SNPs) and aspirin resistance (AR) have been studied with variable results. The associations of genetic variants with AR may be helpful to explain why some individuals demonstrate aspirin insensitivity with this anti-platelet therapy. The purpose of this research was to investigate the effect of different genotypes in candidate genes on aspirin response in patients taking long-term aspirin therapy by measuring the serum thromboxane B2 (TXB2) and platelet function using the Multiplate® analyser. MethodsA total of 266 patients with stable coronary heart disease (CHD) taking low-dose aspirin for long periods of time and without any other anti-platelet drugs medications were enrolled into the study. They were required to take 80 mg of aspirin every morning for a week including the day before blood tests. Blood samples were collected 24 h after the last dose. The 80 mg dose of aspirin was taken orally and blood samples were collected again 1 h later. The serum TXB2 levels were measured in samples at 24 h post-dose and 1 h post-dose using the EIA kit and platelet activity was determined using the Multiplate® Impedance Platelet Aggregometry (ASPI) assay. Genotyping assays were performed by the TaqMan SNP genotyping technique. ResultsOf the 266 patients, only 251 patients were enrolled in the present study. The PTGS1/COX1-1676 A > G (rs1330344) and the PTGS2/COX2-765 G > C (rs20417) SNPs showed significant associations with the ASPI measurements in samples taken at 24 h post-dose, but not with the values at 1 h post-dose or with the TXB2 levels (P < 0.05). ConclusionsOur results suggest that polymorphisms in the PTGS1/COX1 and the PTGS2/COX2 genes may be associated with reduced anti-aggregatory effects and increased the risk of AR, but future larger-scale cohort studies are necessary for further validation.

Potential Association of The Pathogenic Kruppel-like Factor 14 (KLF14) and Adiponectin (ADIPOQ) SNVs with Susceptibility to T2DM.

To evaluate the associations of the pathogenic variants in Kruppel-like Factor 14 (KLF 14) and Adiponectin (ADIPOQ) with susceptibility to type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease characterized by increased blood sugar and caused by resistance to insulin in peripheral tissues and damage to pancreatic beta cells. Kruppel-like Factor 14 (KLF-14) is proposed to be a regulator of metabolic diseases, such as diabetes mellitus (DM) and obesity. Adiponectin (ADIPOQ) is an adipocytokine produced by the adipocytes and other tissues and was reported to be involved in T2DM. To study the possible association of the KLF-14 rs972283 and ADIPOQ-rs266729 with the risk of T2DM in the Saudi population. We have evaluated the association of KLF-14 rs972283 C>T and ADIPOQ-rs266729 C>G SNV with the risk to T2D in the Saudi population using the Amplification Refractory Mutation System PCR (ARMS-PCR), and blood biochemistry analysis. For the KLF-14 rs972283 C>T SNV we included 115 cases and 116 healthy controls, and ADIPOQ-rs266729 C>G SNV, 103 cases and 104 healthy controls were included. Results indicated that the KLF-14 rs972283 GA genotype and A allele were associated with T2D risk with OR=2.14, p-value= 0.014 and OR=1.99, p-value=0.0003, respectively. Results also ADIPOQ-rs266729 CG genotype and C allele were associated with an elevated T2D risk with an OR=2.53, p=0.003 and OR=1.66, p-value =0.012, respectively. We conclude that SNVs in KLF-14 and ADIPOQ are potential loci for T2D risk. Future large-scale studies to verify these findings are recommended. These results need further verifications in protein functional and large-scale case control studies before being introduced for genetic testing.

Exome-wide association study for replication of rare variants affecting the severity of COVID-19 in the Russian population

BACKGROUND: Human genotype is a factor that determines the severity of COVID-19. Previously, a large-scale whole-genome association study of the COVID-19 Host Genetics Initiative (2021) investigated the association of genetic variants at multiple loci with COVID-19 severity. The genetic variants that have the greatest effect on COVID-19 severity are expected to have a low frequency in the population. Therefore, the study of rare variants may provide additional insights into the disease pathogenesis and thus help in the development of prevention and treatment options. AIM: To search for genes enriched for rare genetic variants associated with COVID-19 severity in the Russian population by replication analysis. METHODS: The clinical exome of a Russian cohort of patients was sequenced based on the St. Petersburg State Budgetary Institution “City Hospital No. 40” and St Petersburg University. The study used biomaterial from patients hospitalized at City Hospital No. 40 diagnosed with COVID-19 and healthy individuals (population control group). The severity of the course of COVID-19 was determined according to the results of lung computed tomography. The list of genes for subsequent replication was generated by a literature review. Burden test methods were used for the replication analysis of genes associated with COVID-19 severity. RESULTS: In total, 701 clinical exomes were sequenced from 263 individuals with severe COVID-19 and 438 healthy individuals. In the literature review, 18 genes associated with severe COVID-19 were included in the replication analysis. The replication analysis did not identify any genes whose association with severe COVID-19 was confirmed in the study cohort. CONCLUSION: The replication analysis did not identify any genes that showed a significant association between the functional variant enrichment and COVID-19 severity. However, the direction of the correlation was consistent with the findings of previous studies. Expanding the study cohort would increase the power of the tests and allow us to detect additional rare variants that influence the severity of COVID-19 progression.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.MethodsBuilding on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.ResultsA gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10–39; OR = 4.73, p = 2 × 10–10; OR = 2.3, p = 7.49 × 10–9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10–7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10–16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10–6).ConclusionsIn a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.

Association of genetic variants in soy isoflavones metabolism-related genes with decreased lung cancer risk

BackgroundSoy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer. MethodsA two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk. ResultsA nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57–0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008). ConclusionsWe identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.

Polymorphism in the matrix metallopeptidase genes is associated with coronary artery disease risk with concomitant metabolic syndrome

Background: Metabolic syndrome (MS) and its components are the reasons of the development and progression of cardiovascular diseases. Nowadays, the association between coronary artery disease and MS remains ambiguous. The central role of matrix metallopeptidases (MMP) in the metabolism of connective tissue proteins, cell matrix remodeling, tissue repair and other complex biochemical processes has been shown, which implies their involvement in the pathogenesis of cardiovascular diseases. The aim of the study: To study the associations of polymorphic variants in the MMP genes with the risk of stable coronary artery disease with concomitant metabolic syndrome. Materials and methods: 170 patients with stable coronary artery disease concomitant with a visceral type of obesity in combination with two or more pathological conditions (elevated serum blood glucose level, elevated serum blood cholesterol level, hypertension) were included in the case group. Conditionally healthy volunteers (n=182) were recruited in the control group. Genotyping of five polymorphic sites in the four genes MMP1 (rs514921), MMP3 (rs6796620 and rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) was performed by real-time PCR. The serum blood level of MMP was measured by ELISA. Gene-gene interactions were analyzed using MDR v.3.0.2 software. Results: The frequency of heterozygous C/T genotype in the MMP3 gene (rs626750) was higher in the control group (37.90%) compared to the case group (23.20%), which indicates its protective effect on the risk of coronary artery disease with concomitant metabolic syndrome (OR=0.47, 95%CI 0.29-0.75). 2.6-fold increased risk of coronary artery disease with concomitant metabolic syndrome was demonstrated for carriers of the A/G genotype in the TIMP2 gene (rs2277698) according to the codominant inheritance model. We found no associations of polymorphic variants in the MMP1 (rs514921), MMP3 (rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) genes with the serum blood level of MMP, as well as their inhibitors. Four-loci model of gene-gene interactions (MMP9 (rs17576) – MMP3 (rs626750) – MMP1 (rs514921) – TIMP2 (rs2277698)) characterized by high sensitivity, specificity and risk effect to the coronary artery disease with concomitant metabolic syndrome development was discovered. Conclusion: This study revealed the association of polymorphic variants in the MMP genes and their inhibitors with the risk of coronary artery disease with concomitant metabolic syndrome. In addition, a four-locus model of intergenic interactions with high sensitivity and specificity was obtained.

Rare variants at KCNJ2 are associated with LDL-cholesterol levels in a cross-population study

Leveraging whole genome sequencing data of 1751 individuals from the UK and 2587 Qatari subjects, we suggest here an association of rare variants mapping to the sour taste-associated gene KCNJ2 with reduced low-density lipoprotein cholesterol (LDL-C, P = 2.10 × 10−12) and with a 22% decreased dietary trans-fat intake. This study identifies a novel candidate rare locus for LDL-C, adding insights into the genetic architecture of a complex trait implicated in cardiovascular disease.

Search for molecular markers of joint hypermobility

Background: Joint hypermobility (JH) is a condition that can be either benign or accompanied by pain and early development of osteoarthritis. For early verification of the risk of complications, it is necessary to study the molecular pathogenesis of various JH variants. The aim of the study: The aim of this study was to search for candidate genes involved in connective tissue metabolism and causing joint hypermobility in a form isolated or combined with connective tissue dysplasia (CTD). Materials and methods: The study involved young (21,86±0,22 y.o.) people (n=181). A clinical study was conducted for the presence of signs of JH (Beighton scale) and CTD (tables Kadurina T.I.). Further, a molecular genetic study was carried out and the search for associations of polymorphic variants of genes (vitamin D receptor (VDR), lumican (LUM), tenascin (TNXB), growth/differentiation factor 5 (GDF5), magnesium ion channel TRPM6), bone morphogenetic protein type 5 (BMP5)) and JH, CTD in isolated and combined forms. Statistical data processing was carried out by comparing qualitative features using the χ2 test, Fisher's exact test, and the χ2 test with Yates' correction for contingency tables 2x2. The strength of associations was assessed in terms of the odds ratio (Odds Ratio, OR, at p&lt;0.05), the correction for multiple comparisons was carried out using the FDR method (Benjamin- Hochberg). Quantitative data were evaluated in pairs using the Student's t-test, the normality of distribution according to the Kolmogorov-Smirnov test. Results: Associations of the G allele and the GG genotype of the rs3734444 locus of the BMP5 gene with the presence of JH (OR=3.70 and OR=5.10), the A allele of the rs1470527 locus of the BMP5 gene and the presence of JH+CTD- (OR=8.00), the T allele and the TT genotype of the rs11144134 locus of the TRPM6 gene with JH in isolated (OR=3.00 and OR =10.19) and in the forms combined with CTD (OR=3.17 and OR=11.28), the TT genotype was also associated with the isolated form of CTD (OR=3.74). The GT genotype of the rs73611720 locus of the GDF5 gene was associated with isolated CTD (OR=4.15). No statistically significant associations were found for polymorphic variants rs11540149 (VDR), rs2268578 and rs3759222 (LUM), rs3130342 (TNXB). Conclusion: The G allele of locus rs3734444 of the BMP5 gene is a potential risk marker for JH in general, the A allele of locus rs1470527 is an isolated JH, the GT genotype of locus rs73611720 of the GDF5 gene is a marker for isolated CTD, the T allele of locus rs11144134 of the TRPM6 gene is a marker for JH combined with CTD.

Causal relationship between prostatic diseases and prostate cancer: a mendelian randomization study

BackgroundAlthough it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are unclear.MethodsWe assessed the causal relationship between prostatitis or BPH and PCa using a two-sample Mendelian randomization (MR) approach. The data utilized in this study were sourced from genome-wide association study. The association of genetic variants from cohorts of prostatitis or BPH and PCa patients was determined using inverse-variance weighted and MR Egger regression techniques. The direction of chance was determined using independent genetic variants with genome-wide significance (P < 5 × 10–6). The accuracy of the results was confirmed using sensitivity analyses.ResultsMR analysis showed that BPH had a significant causal effect on PCa (Odds Ratio = 1.209, 95% Confidence Interval: 0.098–0.281, P = 5.079 × 10− 5) while prostatitis had no significant causal effect on PCa (P > 0.05). Additionally, the pleiotropic test and leave-one-out analysis showed the two-sample MR analyses were valid and reliable.ConclusionsThis MR study supports that BPH has a positive causal effect on PCa, while genetically predicted prostatitis has no causal effect on PCa. Nonetheless, further studies should explore the underlying biochemical mechanism and potential therapeutic targets for the prevention of these diseases.

Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis.

Our objective was to evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH)-associated genes among patients with systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS). Targeted sequencing of HLH genes (LYST, PRF1, RAB27A, STX11, STXBP2, UNC13D) was performed in patients with sJIA from an established cohort. Sequence data from control participants were obtained in silico (database of Genotypes and Phenotypes: phs000280.v8.p2). Rare variant association testing (RVT) was performed with sequence kernel association test package. Significance was defined as P < 0.05 after 100,000 permutations. Sequencing data from 524 sJIA cases were jointly called and harmonized with exome-derived target data from 3,000 controls. Quality control operations produced a set of 480 cases and 2,924 ancestrally matched control participants. RVT of cases and controls revealed a significant association with rare protein-altering variants (minor allele frequency [MAF] < 0.01) of STXBP2 (P = 0.020) and ultrarare variants (MAF < 0.001) of STXBP2 (P = 0.006) and UNC13D (P = 0.046). A subanalysis of 32 cases with known MAS and 90 without revealed a significant difference in the distribution of rare UNC13D variants (P = 0.0047) between the groups. Additionally, patients with sJIA more often carried two or more HLH variants than did controls (P = 0.007), driven largely by digenic combinations involving LYST. We identified an enrichment of rare HLH variants in patients with sJIA compared with controls, driven by STXBP2 and UNC13D. Biallelic variation in HLH genes was associated with sJIA, driven by LYST. Only UNC13D displayed enrichment in patients with MAS. This suggests that HLH variants may contribute to the pathophysiology of sJIA, even without MAS.

The influence of gut microbiota on membranous nephropathy: A two-sample Mendelian randomization study.

Therapeutic approaches that target the gut microbiota may be helpful in the potential prevention and treatment of membranous nephropathy (MN). Several studies demonstrated a correlation between gut microbiota and MN. However, the confounding evidence cannot prove a causal relationship between gut microbiota and MN. The aim of our study is to assess genome-wide association study data for a causal relationship between gut microbiota and MN using a two-sample Mendelian randomization (MR) approach. Inverse variance weighted (IVW) was used as the primary technique to determine the association of genetic variants from gut microbiota and MN patients. Besides, sensitivity analyses confirmed the accuracy of the results. Finally, we applied false discovery rate (FDR) correction to results with IVW < 0.05 during multiple hypothesis testing. The results from IVW estimates indicated that Bacillales exhibited a significant association with MN, acting as a risk factor (OR = 1.52, 95% CI: 1.14 - 2.02, p = 0.005). In addition, our univariable MR results showed that 7 bacterial taxa (Melainabacteria, Butyricicoccus, Catenibacterium, Ruminiclostridium5, RuminococcaceaeUCG003, RuminococcaceaeUCG013, and Gastranaerophilales) had suggestive associations with MN. The sensitivity analysis did not reveal any significant heterogeneity in the instrumental variables or horizontal pleiotropy. Our findings provided causal evidence for the effect of gut microbiota on MN patients and broadened the spectrum of bacterial taxa that might be involved in the pathogenesis of MN. These selected bacterial taxa hold promise as new biomarkers, which may aid in designing targeted therapeutic modalities for MN, improving our comprehension of the gut-kidney axis.

Association of Vascular Endothelial Growth Factor (VEGF) and Mouse Model Minute 2 (MDM2) Polymorphisms With Diabetic Retinopathy in a Northwest Indian Population: A Case-Control Study.

Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes (T2D), results from complex interactions of genetic and environmental factors. Vascular endothelial growth factor (VEGF) and mouse model minute 2 (MDM2)are upregulated in the retina due to diabetes, which increases the risk of DR. VEGFA and MDM2 genetic variations can influence DR risk. The present case-control study was conducted to evaluate the association of VEGFA and MDM2 promoter variants with DR in a population from Punjab, Northwest India. A total of 414 DR patients, 425 T2D patients without DR, and 402 healthy controls were screened for VEGFA -2578C/A (rs699947), VEGFA -2549I/D (rs35569394), VEGFA -7C/T (rs25648), and MDM2 rs3730485 polymorphisms using polymerase chain reaction (PCR)-based methods. VEGFA -2549 I allele (OR = 1.35 (1.00-1.81), p = 0.043) and II genotype (OR = 1.78 (1.00-3.15), p = 0.047) were significantly associated with increased risk of DR. VEGFA -7 CT genotype conferred reduced risk of DR (OR = 0.28 (0.20-0.38); p = <0.001). VEGFA -2578 and MDM2 rs3730485 showed no significant association with DR. A-I-T (OR = 0.30 (0.20-0.44); p = <0.001) and C-D-T (OR = 0.33 (0.16-0.65); p = 0.002) haplotypes of rs699947-rs35569394-rs25648 polymorphisms showed decreased risk of DR. I allele and II genotype of VEGFA -2549, CT genotype of VEGFA -7, and C-I-C and A-D-C haplotypes of rs699947-rs35569394-rs25648 polymorphisms were significantly associated with DR risk in a Northwest Indian population. This is the first study worldwide to report DR risk with VEGFA promoter variants together.

Association of ORMDL3 single nucleotide polymorphic variants with bronchial asthma in Pathan population

BackgroundSingle nucleotide polymorphic variants of chromosome 17q21 potential candidate genes have been found to associate with asthma predisposition in many ethnically diverse populations. Identifying the potential SNPs, that are associated with asthma in a certain population, may lead to early diagnosis of genetic predisposition, thus reducing the treatment cost by timely management. This research work was planned to study the association of SNPs residing on chromosome 17q21, with asthma, in the Pathan population of Pakistan. MethodsSixty- two physician-diagnosed bronchial asthma cases and one hundred, age and gender-matched, control subjects of the Pathan ethnic group were enrolled for this study. Five SNPs from 17q21 were analyzed for their association with asthma by the Single Base Extension method using capillary-based electrophoresis. Allelic, dominant and recessive genotypic association analyses were done by PLINK and SHEsis plus version beta software, followed by Haploview v4.1 analysis of relevant haplotypes. ResultsOut of five studied SNPs, rs8076131 was significantly associated with bronchial asthma whereas rs9894164 tended to show a marginal association. Haplotype ‘TATT’ seemed to be a marginal risk factor associated with bronchial asthma in the studied population. Conclusionrs8076131 may be used as a predictive indicator of Bronchial Asthma development in risk allele carriers of Pathan ethnicity.

Rare variant association analyses reveal the significant contribution of carbohydrate metabolic disturbance in severe adolescent idiopathic scoliosis

BackgroundAdolescent idiopathic scoliosis (AIS), the predominant genetic-influenced scoliosis, results in spinal deformities without vertebral malformations. However, the molecular aetiology of AIS remains unclear.MethodsUsing genome/exome sequencing, we studied 368 patients with...

Genetic variants of LEAP2 are associated with anthropometric traits and circulating insulin-like growth factor-1 concentration: A UK Biobank study.

To test the hypothesis that liver-expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity. Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin-like growth factor-1 (IGF-1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex-stratified analyses were also conducted. Five SNPs showed positive associations with obesity-related traits. rs57880964 was associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF-1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF-1 concentration in both sexes. These findings reveal sex-specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF-1 concentration.

Association of single nucleotide variants of the TCF7L2, FABP2, FTO, DRD2, MC4R genes with morbid obesity in women

BACKGROUND: Obesity is a widespread disease associated with serious complications. Obesity is a risk factor for many chronic diseases. The most common type of obesity is polygenic obesity, the pathogenesis of which involves external and internal factors, including genetic ones.AIM: Search and study of the association of variants of the nucleotide sequence rs9939609 of the FTO gene, rs7903146 of the TCF7L2 gene, rs1799883 of the FABP2 gene, rs1800497 of the DRD2 gene, rs17782313 of the MC4R gene with morbid obesity in women.MATERIALS AND METHODS: Study design is case-control study. The morbid obesity group and the control group were formed from the DNA bank of participants of the international project HAPIEE. Genotyping was performed by PCR-RFLP and real-time PCR (TaqMan probes, Applied Biosystems, USA). Statistical analysis was performed in SPSS software using Pearson’s chi-square test, Fisher’s exact two-tailed test with Yates’ correction for continuity. The significance level was used p&lt;0.05.RESULTS: Morbid obesity group included 192 women (mean age 57.02± .16 years) with BMI over 40 kg/m2, control group included 450 women (mean age 55.44±7.41 years) with normal BMI (18.5-24.9 kg/m2). There were no statistically significant differences between the groups in the frequencies of genotypes and alleles rs7903146 of the TCF7L2 gene, rs1799883 of the FABP2 gene, rs1800497 of the DRD2 gene (p&gt;0.05). In the group of morbid obesity, the proportion of carriers of the TT genotype rs9939609 of the FTO gene was statistically significantly lower, and the AT genotype was significantly higher than in the control group (OR=0.579, 95% CI 0.399-0.840, p=0.004; OR=1.408, 95% CI 1.003- 1.976, p=0.047, respectively). The heterozygous TC genotype rs17782313 of the MC4R gene is statistically significantly more common (OR=1.825, 95% CI 1.257-2.652, p=0.002), while the homozygous TT genotype is less common (OR=0.500, 95% CI 0.346-0.723, p&lt;0.001) in group of morbid obesity compared with the control group.CONCLUSION: Heterozygous genotypes of the rs9939609 of the FTO gene (AT) and rs17782313 of the MC4R gene (TC) are risk genotypes; the homozygous genotype TT of the variants is protective for morbid obesity in women. Single nucleotide variants rs7903146 of the TCF7L2 gene, rs1799883 of the FABP2 gene, and rs1800497 of the DRD2 gene are not associated with morbid obesity in women.

Exploring the association of FTO rs9939609 and SIRT1 rs7069102 genetic variants with obesity: A case–control study in a sample of Pakistani population

Exploring the association of FTO rs9939609 and SIRT1 rs7069102 genetic variants with obesity: A case–control study in a sample of Pakistani population

Association of HLA variants and related SNPs with sarcoidosis and its phenotypes in the Greek patients

Association of HLA variants and related SNPs with sarcoidosis and its phenotypes in the Greek patients

Genetic variants related to insulin metabolism are associated with gestational diabetes mellitus

The current study sought to investigate the associations of common genetic risk variants with gestational diabetes mellitus (GDM) risk in the north Indian population and to evaluate their utility in identifying GDM cases. A case-control study, including 300 pregnant women, was included, and clinical and pathological information was collected. The amplification-refractory mutation system (ARMS) was used for genotyping four single nucleotide polymorphisms (SNPs), namely FTO (rs9939609), PPARG2 (rs1801282), SLC30A8 (rs13266634), and TCF7L2 (rs12255372). The odds ratio and confidence interval were determined for each SNP in different genetic models. Further, attributable risk, population penetrance, and relative risk were also calculated. The risk allele A of FTO (rs9939609) poses a two times higher risk of GDM (p = 0.02, OR = 2.5). The CG and GG genotypes of PPARG2 (rs1801282) have half a lower risk of GDM. In SLC30A8 (rs13266634), the recessive model analysis showed a two times higher risk of having GDM, while the recessive model (TT vs. GG + GT) analysis in TCF7L2 (rs12255372) indicates a lower risk of GDM. Finally, the relative risk, population penetrance, and attributable risk for risk allele in all four variants was higher in GDM mothers. All four polymorphisms were found to be significantly associated with BMI, HbA1c, and insulin. Our study first time confirmed a significant association with GDM for four variants, FTO, PPARG2, SLC30A8, and TCF7L2, in the North Indian population.

Occupational noise and genetic variants in stress hormone biosynthesis-based genes and rates of blood lipid changes in China: A five-year longitudinal study

Lipid profiles are influenced by both noise and genetic variants. However, little is known about the associations of occupational noise and genetic variants with age-related changes in blood lipids, a crucial event in the initiation and evolution of atherosclerotic cardiovascular diseases. We aimed to evaluate the associations of blood lipid change rates with occupational noise and genetic variants in stress hormone biosynthesis-based genes. This cohort was established in 2012 and 2013 and was followed up until 2017. A total of 952 participants were included in the final analysis and all of them were categorized to two groups, the exposed group and control group, according to the exposed noise levels in their working area. Single nucleotide polymorphisms (SNPs) in stress hormone biosynthesis-based genes were genotyped. Five physical examinations were conducted from 2012 to 2017 and lipid measurements were repeated five times. The estimated annual changes (EACs) of blood lipid were calculated as the difference in blood lipid levels between any 2 adjacent examinations divided by their time interval (year). The generalized estimating equations for repeated measures analyses with exchangeable correlation structures were used to evaluate the influence of exposing to noise (versus being a control) and the SNPs mentioned above on the EACs of blood lipids. We found that the participants experienced accelerated age-related decline in high-density lipoprotein cholesterol (HDL-C) levels as they were exposed to noise (β = −0.38, 95% confidence interval (CI), −0.66 to −0.10, P = 0.007), after adjusting for work duration, gender, smoking, alcohol consumption, and pack-years. This trend was only found in participants with COMT-rs165815 TT genotype (β = −1.19, 95% CI, −1.80 to −0.58, P < 0.001), but not in those with the CC or CT genotypes. The interaction of noise exposure and rs165815 was marginally significant (Pinteraction = 0.010) after multiple adjustments. Compared with DDC-rs11978267 AA genotype carriers, participants carrying rs11978267 GG genotype had decreased EAC of triglycerides (TG) (β = −5.06, 95% CI, −9.07 to −1.05, P = 0.013). Participants carrying DBH-rs4740203 CC genotype had increased EAC of total cholesterol (TC) (β = 1.19, 95% CI, 0.06 to 2.33, P = 0.039). However, these findings were not statistically significant after multiple adjustments. These results indicated that Occupational noise exposure was associated with accelerated age-related decreases in HDL-C levels, and the COMT-rs165815 genotype appeared to modify the effect of noise exposure on HDL-C changes among the occupational population.