Dataset Information

Association Analysis of the HNF4A Common Genetic Variants with Type 2 Diabetes Mellitus Risk.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is a complex disease that involves a wide range of genetic and environmental factors. The hepatocyte nuclear factor (HNF4A) carries out hepatic gluconeogenesis regulation and insulin secretion crucially, and the corresponding gene was shown to be linked to T2DM in several studies. The aim of the present study was to evaluate the association between HNF4A genetic variants (rs1884613 and rs1884614) and T2DM risk in a group of Iranian patients. This case-control study included 100 patients with T2DM and 100 control subjects. Genotyping of two single nucleotide polymorphisms (SNPs) (rs1884613 and rs1884614) of HNF4A was performed using the sequencing method. There was no statistically significant difference for allele and genotype distribution of the HNF4A common variants (rs1884613 and rs1884614) between subjects with and without T2DM (P=0.9 and P=0.9, respectively). Regarding diabetic complications, although the presence of mentioned polymorphisms increased the odds of developing ophthalmic complications and reduction of the odds of renal complications among diabetic patients, the mentioned risk was non- significant and cannot be generalized to the whole population. It seems that rs1884613 and rs1884614 polymorphisms are not associated with T2DM or its renal and ophthalmic complications. To investigate the precise influence of these polymorphisms, prospective cohorts with larger sample sizes are required.

SUBMITTER: Azizi SM

PROVIDER: S-EPMC7175614 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association Analysis of the HNF4A Common Genetic Variants with Type 2 Diabetes Mellitus Risk.

Azizi Seyedeh Mina SM Sarhangi Negar N Afshari Mahdi M Abbasi Davood D Aghaei Meybodi Hamid Reza HR Hasanzad Mandana M

International journal of molecular and cellular medicine 20190828 Suppl1

Type 2 diabetes mellitus (T2DM) is a complex disease that involves a wide range of genetic and environmental factors. The <i>hepatocyte nuclear factor (HNF4A)</i> carries out hepatic gluconeogenesis regulation and insulin secretion crucially, and the corresponding gene was shown to be linked to T2DM in several studies. The aim of the present study was to evaluate the association between <i>HNF4A</i> genetic variants (rs1884613 and rs1884614) and T2DM risk in a group of Iranian patients. This cas ...[more]

PMID: 32351910

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Project description:ObjectiveWe aimed to explore the associations between common genetic risk variants with gestational diabetes mellitus (GDM) risk in Russian women and to assess their utility in the identification of GDM cases.MethodsWe conducted a case-control study including 1,142 pregnant women (688 GDM cases and 454 controls) enrolled at Almazov National Medical Research Centre. The International Association of Diabetes and Pregnancy Study Groups criteria were used to diagnose GDM. A total of 11 single- nucleotide polymorphisms (SNPs), including those in HKDC1 (rs10762264), GCK (rs1799884), MTNR1B (rs10830963 and rs1387153), TCF7L2 (rs7903146 and rs12255372), KCNJ11 (rs5219), IGF2BP2 (rs4402960), IRS1 (rs1801278), FTO (rs9939609), and CDKAL1 (rs7754840) were genotyped using Taqman assays. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). A simple-count genetic risk score (GRS) was calculated using 6 SNPs. The area under the receiver operating characteristic curve (c-statistic) was calculated for the logistic regression model predicting the risk of GDM using clinical covariates, SNPs that had shown a significant association with GDM in our study, GRS, and their combinations.ResultsTwo variants in MTNR1B (rs1387153 and rs10830963) demonstrated a significant association with an increased risk of GDM. The association remained significant after adjustment for age, pre-gestational BMI, arterial hypertension, GDM in history, impaired glucose tolerance, polycystic ovary syndrome, family history of diabetes, and parity (P = 0.001 and P < 0.001, respectively). After being conditioned by each other, the effect of rs1387153 on GDM predisposition weakened while the effect of rs10830963 remained significant (P = 0.004). The risk of GDM was predicted by clinical variables (c-statistic 0.712, 95 % CI: 0.675 - 0.749), and the accuracy of prediction was modestly improved by adding GRS to the model (0.719, 95 % CI 0.682 - 0.755), and more by adding only rs10830963 (0.729, 95 % CI 0.693 - 0.764).ConclusionAmong 11 SNPs associated with T2D and/or GDM in other populations, we confirmed significant association with GDM for two variants in MTNR1B in Russian women. However, these variants showed limited value in the identification of GDM cases.

Project description:SIRT1 has been demonstrated in nutrient-sensing and insulin-signaling pathways in in vivo and in vitro experiments, but there is minimal information concerning the association between gene polymorphisms of SIRT1 and type 2 diabetes mellitus (T2DM) in a Chinese Han population. Using case-control design, we recruited 310 unrelated T2DM patients from inpatients at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, while 301 healthy controls were volunteers from the community for regular medical checkup. All participants were genotyped within the SIRT1 region. The following five SNPs rs10509291, rs12778366, rs10997870, rs10823112, and rs4746720 cover 100% of common genetic variations (minor allele frequency≥0.05) within the SIRT1 gene (r2≥0.8). The genotypes of SIRT1 gene polymorphisms were analyzed by the Snapshot assay and DNA sequencing. The resulting data show that there was significant genetic differentiation in rs10823112 [p=0.003; OR (95% CI)=1.515 (1.152-1.994) for genotype], rs4746720 [p=0.024; OR (95% CI)=1.37 (1.037-1.674) for genotype], and rs10509291 [p=0.002; OR (95% CI)=1.551 (1.179-2.04) for genotype] between T2DM and control subjects. However, the result of rs4746720 was no longer significant after correction for multiple testing (p after Bonferroni correction=0.12); the results of rs10509291and rs10823112 were still significantly different between the two groups (p after Bonferroni correction=0.01 and 0.015, respectively). Linear regression analyses adjusting for age, gender, and body mass index (BMI) showed that HbA1c and HOMA-IR in subjects with rs10509291 AA genotype were higher than those with TT genotype in T2DM group (p=0.045, p=0.035, respectively). Together, our data show that genetic variation of the SIRT1 gene is related to insulin resistance and increase risk of T2DM in Chinese Han population. The risk allele A at SIRT1 rs10509291 was closely associated with T2DM, and subjects who were homozygous of the A allele were more likely to develop T2DM.

Dataset Information

Association Analysis of the HNF4A Common Genetic Variants with Type 2 Diabetes Mellitus Risk.

Publications

Association Analysis of the HNF4A Common Genetic Variants with Type 2 Diabetes Mellitus Risk.

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