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Genetic association of ADIPOQ gene variants (-3971A>G and +276G>T) with obesity and metabolic syndrome in North Indian Punjabi population.

ABSTRACT: BACKGROUND AND AIMS:At 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. METHODS:Biochemical 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. RESULTS:All 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. CONCLUSION:The 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.

SUBMITTER: Kaur H

PROVIDER: S-EPMC6161880 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Genetic association of ADIPOQ gene variants (-3971A>G and +276G>T) with obesity and metabolic syndrome in North Indian Punjabi population.

Kaur Harjit H Badaruddoza Badaruddoza B Bains Veena V Kaur Anupam A

PloS one 20180928 9

<h4>Background and aims</h4>At 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 var ...[more]

PMID: 30265726

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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: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?<?0.025). SNPs rs7607980 near COBLL1 (p?=?0.0001), rs13389219 near GRB14 (p?=?0.026) and rs10423928 in the GIPR gene (p?=?0.012) as well as the genetic risk score (GRS) for these previously shown insulin resistance loci here associated with insulin resistance defined by HOMA2-IR and showed a trend towards GDM. GRS comprised of 3 insulin secretion loci here associated with insulin secretion but not GDM. CONCLUSIONS:GDM in women from Punjab in Northern India shows a genetic component, seemingly driven by insulin resistance and secretion and partly shared with GDM in other parts of the world. Most previous T2D loci discovered in European studies did not associate with GDM in North India, indicative of different genetic etiology or alternately, differences in the linkage disequilibrium (LD) structure between populations in which the associated SNPs were identified and Northern Indian women. Interestingly some T2D risk variants were in fact indicative of being protective for GDM in these Indian women.

Dataset Information

Genetic association of ADIPOQ gene variants (-3971A>G and +276G>T) with obesity and metabolic syndrome in North Indian Punjabi population.

Publications

Genetic association of ADIPOQ gene variants (-3971A>G and +276G>T) with obesity and metabolic syndrome in North Indian Punjabi population.

Similar Datasets

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