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Common variants of ARID1A and KAT2B are associated with obesity in Indian adolescents.

ABSTRACT: Obesity involves alterations in transcriptional programs that can change in response to genetic and environmental signals through chromatin modifications. Since chromatin modifications involve different biochemical, neurological and molecular signaling pathways related to energy homeostasis, we hypothesize that genetic variations in chromatin modifier genes can predispose to obesity. Here, we assessed the associations between 179 variants in 35 chromatin modifier genes and overweight/obesity in 1283 adolescents (830 normal weight and 453 overweight/obese). This was followed up by the replication analysis of associated signals (18 variants in 8 genes) in 2247 adolescents (1709 normal weight and 538 overweight/obese). Our study revealed significant associations of two variants rs6598860 (OR?=?1.27, P?=?1.58?×?10-4) and rs4589135 (OR?=?1.22, P?=?3.72?×?10-4) in ARID1A with overweight/obesity. We also identified association of rs3804562 (??=?0.11, P?=?1.35?×?10-4) in KAT2B gene with BMI. In conclusion, our study suggests a potential role of ARID1A and KAT2B genes in the development of obesity in adolescents and provides leads for further investigations.

SUBMITTER: Giri AK

PROVIDER: S-EPMC5834613 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Common variants of ARID1A and KAT2B are associated with obesity in Indian adolescents.

Giri Anil K AK Parekatt Vaisak V Dwivedi Om Prakash OP Banerjee Priyanka P Bandesh Khushdeep K Prasad Gauri G Tandon Nikhil N Bharadwaj Dwaipayan D

Scientific reports 20180302 1

Obesity involves alterations in transcriptional programs that can change in response to genetic and environmental signals through chromatin modifications. Since chromatin modifications involve different biochemical, neurological and molecular signaling pathways related to energy homeostasis, we hypothesize that genetic variations in chromatin modifier genes can predispose to obesity. Here, we assessed the associations between 179 variants in 35 chromatin modifier genes and overweight/obesity in ...[more]

PMID: 29500370

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Project description:BackgroundPrevious genome-wide association studies for type 2 diabetes susceptibility genes have confirmed that a common variant, rs9939609, in the fat mass and obesity associated (FTO) gene region is associated with body mass index (BMI) in European children and adults. A significant association of the same risk allele has been described in Asian adult populations, but the results are conflicting. In addition, no replication studies have been conducted in children and adolescents of Asian ancestry.MethodsA population-based survey was carried out among 3503 children and adolescents (6-18 years of age) in Beijing, China, including 1229 obese and 2274 non-obese subjects. We investigated the association of rs9939609 with BMI and the risk of obesity. In addition, we tested the association of rs9939609 with weight, height, waist circumference, waist-to-height ratio, fat mass percentage, birth weight, blood pressure and related metabolic traits.ResultsWe found significant associations of rs9939609 variant with weight, BMI, BMI standard deviation score (BMI-SDS), waist circumference, waist-to-height ratio, and fat mass percentage in children and adolescents (p for trend = 3.29 x 10-5, 1.39 x 10-6, 3.76 x 10-6, 2.26 x 10-5, 1.94 x 10-5, and 9.75 x 10-5, respectively). No significant associations were detected with height, birth weight, systolic and diastolic blood pressure and related metabolic traits such as total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and fasting plasma glucose (all p > 0.05). Each additional copy of the rs9939609 A allele was associated with a BMI increase of 0.79 [95% Confidence interval (CI) 0.47 to 1.10] kg/m2, equivalent to 0.25 (95%CI 0.14 to 0.35) BMI-SDS units. This rs9939609 variant is significantly associated with the risk of obesity under an additive model [Odds ratio (OR) = 1.29, 95% CI 1.11 to 1.50] after adjusting for age and gender. Moreover, an interaction between the FTO rs9939609 genotype and physical activity (p < 0.001) was detected on BMI levels, the effect of rs9939609-A allele on BMI being (0.95 +/- 0.10), (0.77 +/- 0.08) and (0.67 +/- 0.05) kg/m2, for subjects who performed low, moderate and severe intensity physical activity.ConclusionThe FTO rs9939609 variant is strongly associated with BMI and the risk of obesity in a population of children and adolescents in Beijing, China.

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Common variants of ARID1A and KAT2B are associated with obesity in Indian adolescents.

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Common variants of ARID1A and KAT2B are associated with obesity in Indian adolescents.

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