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Genetic variant of AMD1 is associated with obesity in urban Indian children.

ABSTRACT: Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI). We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children.We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW) and 463 over-weight/obese (OW/OB) children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB) in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR?=?1.41, P?=?1.5×10(-4)] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR?=?1.28, P?=?4.2×10(-3)] and meta-analysis [OR?=?1.35, P?=?1.9×10(-6)]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis.Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.

SUBMITTER: Tabassum R

PROVIDER: S-EPMC3322123 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genetic variant of AMD1 is associated with obesity in urban Indian children.

Tabassum Rubina R Jaiswal Alok A Chauhan Ganesh G Dwivedi Om Prakash OP Ghosh Saurabh S Marwaha Raman K RK Tandon Nikhil N Bharadwaj Dwaipayan D

PloS one 20120409 4

<h4>Background</h4>Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI). We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity i ...[more]

PMID: 22496743

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Project description:Background:Obesity is defined as an abnormal or excessive accumulation of body fat and it is currently one of the most concerning public health issues, as it is related to a wide range of serious diseases and disorders. The study of the causes of obesity is multifactorial, and its diagnosis requires specific methods. Its management is complex, and it is crucial that it is handled appropriately, and its primary focus should be on prevention through lifestyle changes.The objectives of this study are to determine the prevalence of overweight/obesity in adolescents of both genders, aged 10 to 12 years, from different geographical environments (rural and urban), as well as to identify the underlying risk factors related to the respective obesity rates, namely: family environment, eating habits, and physical exercise. Methods:An observational, cross-sectional study in a sample of 129 adolescents aged 10 to 12 years was conducted. Participants of both genders from rural and urban environments were included in this study. A questionnaire was completed on eating habits and physical activity, focusing on the number of daily meals, meal composition, and sedentary lifestyle habits. An anthropometric assessment was also performed, including weight, height, skinfolds, waist circumference, arm circumference, and percentage of lean mass and body fat, using bioelectrical impedance analysis. Results:In the rural environment, the obesity rate was 16.9%, with 26.8% being either overweight or obese; whereas in the urban environment, these rates were respectively 16.7% and 33.4%. Living in a rural environment was not an independent predictor of being overweight or obesity, p?=?0.581, or for increased percentage of body fat, p?=?0.790. In contrast, being 12 years old, eating high-calorie foods four times a week or less, and having at least one obese parent were predictors of being overweight or obesity. Being 12 years old was also a predictor of gaining moderate to high body fat. Conclusions:Adolescents' residence in a rural or urban environment does not affect the occurrence of being overweight, obesity or high body fat. Paternal obesity was an important predictor of obesity in children. Obese fathers tended to serve higher calorie meals to their children.

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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Genetic variant of AMD1 is associated with obesity in urban Indian children.

Publications

Genetic variant of AMD1 is associated with obesity in urban Indian children.

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