Dataset Information

Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women.

ABSTRACT: BACKGROUND:Gestational diabetes (GDM) is a more common problem in India than in many other parts of the world but it is not known whether this is due to unique environmental factors or a unique genetic background. To address this question we examined whether the same genetic variants associated with GDM and Type 2 Diabetes (T2D) in Caucasians also were associated with GDM in North Indian women. METHODS:Five thousand one hundred pregnant women of gestational age 24-28 weeks from Punjab were studied by a 75 g oral glucose tolerance test (OGTT). GDM was diagnosed by both WHO1999 and 2013 criteria. 79 single nucleotide polymorphisms (SNPs) previously associated with T2D and glycemic traits (12 of them also with GDM) and 6 SNPs from previous T2D associations based on Indian population (some also with European) were genotyped on a Sequenom platform or using Taqman assays in DNA from 4018 women. RESULTS:In support of previous findings in Caucasian GDM, SNPs at KCJN11 and GRB14 loci were nominally associated with GDM1999 risk in Indian women (both p?=?0.02). Notably, T2D risk alleles of the variant rs1552224 near CENTD2, rs11708067 in ADCY5 and rs11605924 in CRY2 genes associated with protection from GDM regardless of criteria applied (p?

SUBMITTER: Arora GP

PROVIDER: S-EPMC6083526 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women.

Arora Geeti P GP Almgren Peter P Brøns Charlotte C Thaman Richa G RG Vaag Allan A AA Groop Leif L Prasad Rashmi B RB

BMC medical genomics 20180808 1

<h4>Background</h4>Gestational diabetes (GDM) is a more common problem in India than in many other parts of the world but it is not known whether this is due to unique environmental factors or a unique genetic background. To address this question we examined whether the same genetic variants associated with GDM and Type 2 Diabetes (T2D) in Caucasians also were associated with GDM in North Indian women.<h4>Methods</h4>Five thousand one hundred pregnant women of gestational age 24-28 weeks from Pu ...[more]

PMID: 30089489

Similar Datasets

Project description:BACKGROUND: This study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women. METHODS: A total of 1,985 pregnant Han Chinese women were recruited and evaluated for gestational glucose tolerance status with a two-step approach. The four MTNR1B variants rs10830963, rs1387153, rs1447352, and rs2166706 which had been reported to associate with glucose levels in general non-pregnant populations, were genotyped in these women. Using an additive model adjusted for age and body mass index (BMI), association of these variants with gestational fasting and postprandial plasma glucose (FPG and PPG) levels were analyzed by multiple linear regression; relative risk of developing gestational glucose intolerance was calculated by logistic regression. Hardy-Weinberg Equilibrium was tested by Chi-square and linkage disequilibrium (LD) between these variants was estimated by measures of D' and r(2). RESULTS: In the pregnant Chinese women, the MTNR1B variant rs10830963, rs1387153, rs2166706 and rs1447352 were shown to be associated with the increased 1 hour PPG level (p=8.04 × 10(-10), 5.49 × 10(-6), 1.89 × 10(-5) and 0.02, respectively). The alleles were also shown to be associated with gestational glucose intolerance with odds ratios (OR) of 1.64 (p=8.03 × 10(-11)), 1.43 (p=1.94 × 10(-6)), 1.38 (p=1.63 × 10(-5)) and 1.24 (p=0.007), respectively. MTNR1B rs1387153, rs2166706 were shown to be associated with gestational FPG levels (p=0.04). Our data also suggested that, the LD pattern of these variants in the studied women conformed to that in the general populations: rs1387153 and rs2166706 were in high LD, they linked moderately with rs10830963, but might not linked with rs1447352;rs10830963 might not link with rs1447352, either. In addition, the MTNR1B variants were not found to be associated with any other traits tested. CONCLUSIONS: The MTNR1B is likely to be involved in the regulation of glucose homeostasis during pregnancy.

Project description:Background: A heavy burden of cardiometabolic conditions on low- and middle-income countries like India that are rapidly undergoing urbanization remains unaddressed. Indians are known to have high levels of triglycerides and low levels of HDL-C along with moderately higher levels of LDL-C. The genome-wide findings from Western populations need to be validated in an Indian context for a better understanding of the underlying etiology of dyslipidemia in India. Objective: We aim to validate 12 genetic variants associated with lipid levels among rural and urban Indian populations and derive unweighted and weighted genetic risk scores (uGRS and wGRS) for lipid levels among the Indian population. Methods: Assuming an additive model of inheritance, linear regression models adjusted for all the possible covariates were run to examine the association between 12 genetic variants and total cholesterol, triglycerides, HDL-C, LDL-C, and VLDL-C among 2,117 rural and urban Indian participants. The combined effect of validated loci was estimated by allelic risk scores, unweighted and weighted by their effect sizes. Results: The wGRS for triglycerides and VLDL-C was derived based on five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs2293889 at TRPS1, rs4148005 at ABCA8, and rs4420638 at APOC1), which was associated with 36.31 mg/dL of elevated triglyceride and VLDL-C levels (β = 0.95, SE = 0.16, p < 0.001). Similarly, every unit of combined risk score (rs2293889 at TRPS1 and rs4147536 at ADH1B) was associated with 40.62 mg/dL of higher total cholesterol (β = 1.01, SE = 0.23, p < 0.001) and 33.97 mg/dL of higher LDL-C (β = 1.03, SE = 0.19, p < 0.001) based on its wGRS (rs2293889 at TRPS1, rs4147536 at ADH1B, rs4420638 at APOC1, and rs660240 at CELSR2). The wGRS derived from five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs4148005 at ABCA8, rs4420638 at APOC1, and rs7832643 at PLEC) was associated with 10.64 mg/dL of lower HDL-C (β = -0.87, SE = 0.14, p < 0.001). Conclusion: We confirm the role of eight genome-wide association study (GWAS) loci related to different lipid levels in the Indian population and demonstrate the combined effect of variants for lipid traits among Indians by deriving the polygenic risk scores. Similar studies among different populations are required to validate the GWAS loci and effect modification of these loci by lifestyle and environmental factors related to urbanization.

Project description:The influence of human genetic variants on the vaginal bacterial traits (VBTs) of pregnant women is still unknown. Using a genome-wide association approach based on the 16S rRNA bacteriome analysis, a total of 72 host genetic variant (single nucleotide polymorphisms [SNPs], indels, or copy number variations [CNVs])-VBT associations were found that reached the genome-wide significance level (P < 5 × 10-8) with an acceptable genomic inflation factor λ of <1.1. The majority of these SNPs that reached the genome-wide significance level had a relatively low minor allele frequency (MAF), and only seven of them had MAFs greater than 0.05. rs303212, located at the IFIT1 gene on chromosome 10, was the most eye-catching variant, which had a genome-wide association with the relative abundance (RAB) of Actinobacteria and Bifidobacteriaceae and also had a suggestive association with the RAB of a few common vaginal bacteria including Actinobacteriota, Firmicutes, Lactobacillus, and Gardnerella vaginalis and the beta diversity weighted UniFrac (P < 1 × 10-5). The findings of the study suggest that the vaginal bacteriome may be influenced by a number of genetic variants across the human genome and that interferon signaling may have an important influence on vaginal bacterial communities during pregnancy. IMPORTANCE Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics. We utilized a genome-wide approach to identify the associations between genetic variants and multiple VBTs and performed enrichment analyses. The human genetics during pregnancy may be involved in multiple pathways. The results may disclose innate functional factors involved in shaping the vaginal bacteriome during pregnancy and provide insight into the establishment of specific strategies for prevention and clinical treatment of pregnancy complications.

Project description:Background and aimsAt present obesity and metabolic syndrome (MetS) in India are the most challenging health problems. It is also well accepted that obesity is a significant risk factor for the development of metabolic syndrome and other degenerative diseases. Many studies have reported that single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) gene have been associated with obesity and its related disorders. Here, we aimed to investigate the association of two intronic variants in ADIPOQ gene, -3971A>G (rs822396) and +276G>T (rs1501299) with obesity and metabolic syndrome.MethodsBiochemical and anthropometric measurements were obtained from a total of 550 unrelated subjects (obese = 250 and non-obese = 300) of North Indian Punjabi population. Genotyping for the intron variants were performed by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) methods. After genotyping, as a quality control measure 10% of the samples for each polymorphism were confirmed by Sanger Sequencing method. The distributions of genotypic and allelic frequencies among obese and non-obese groups were compared by chi-square test and the corresponding risk was calculated using binary logistic regression. The effects of multiple testing were controlled by applying Bonferroni corrections.ResultsAll the anthropometric and biochemical parameters except triglycerides (TG) and very low-density lipoproteins cholesterol (VLDL-C) have shown significant association with both GG and TT genotypes of -3971A>G (rs822396) and +276G>T (rs1501299) polymorphisms respectively. The frequencies of GG (-3971A>G) and TT (+276G>T) genotypes were higher among obese cases (p = 0.008 and p = 0.035 respectively). However, no significant association was found between allelic frequencies of ADIPOQ rs822396 and obesity, whereas the association of ADIPOQ rs1501299 attenuated and became marginally significant after Bonferroni correction (p>0.025). Both the variant genotypes of ADIPOQ gene polymorphisms (-3971GG and +276TT) significantly increased the risk of development of obesity (OR: 1.52, p = 0.03; OR: 1.58, p = 0.04 respectively) and MetS (OR: 1.42, p = 0.03; OR: 1.57, p = 0.01 respectively) in the present population, after adjusting the various covariates. The G-T haplotype model (possessing -3971G and +276T alleles) was shown toprovide ~ 3 fold risk towards the obesity susceptibility (OR: 2.69, p = 0.009) and MetS risk (OR: 2.73, p = 0.009) and the association persisted after adjusting for different confounding variables.ConclusionThe present study has confirmed that ADIPOQ -3971A>G (rs822396) and +276G>T (rs1501299) polymorphism may be clinically helpful to estimate obesity and MetS risk in North Indian Punjabi population.

Dataset Information

Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women.

Publications

Association between genetic risk variants and glucose intolerance during pregnancy in north Indian women.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets