Abstract

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 × 10-5, 1.39 × 10-6, 3.76 × 10-6, 2.26 × 10-5, 1.94 × 10-5, and 9.75 × 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.

Highlights

  • Previous 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

  • Several promising genes have been reported to be associated with a variation in body mass index (BMI) in a monogenic or polygenic manner: proprotein convertase subtilisin/kexin type 1 (PCSK1) [6], melanocortin 4 receptor (MC4R) [7], catenin beta-like 1 (CTNNBL1) [8], ectonucleotide pyrophosphatase 1 (ENPP1) [9], and beta 2-adrenergic receptor (ADRB2) [10]

  • The single nucleotide polymorphism (SNP) is associated with fat mass percentage (FMP), waist circumference (WC), WHtR, Systolic BP (SBP) and diastolic BP (DBP) after adjusting for age and gender(p < 0.05 for all traits)

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Summary

Introduction

Previous 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. Frayling et al [11] identified a common variant (rs9939609) in the fat mass and obesity associated (FTO) gene region that represents a T to A change in the first intron of the FTO gene on chromosome 16 They found that there were significant associations of this single nucleotide polymorphism (SNP) with BMI (p = 3 × 10-35) and the risk of obesity [Odds ratio (OR) = 1.67, 95% Confidence interval (CI) 1.47 to 1.89, p = 1 × 10-14 for the homozygous condition] in a European adult population.

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