Common Variation in the Fat Mass and Obesity-Associated (FTO) Gene Confers Risk of Obesity and Modulates BMI in the Chinese Population.

OBJECTIVE--Genetic variants in the fat mass and obesity-associated (FTO) gene have been linked with obesity and type 2 diabetes in European populations. We aimed to test the role of FTO genetic variants in obesity and type 2 diabetes in the Chinese population. RESEARCH DESIGN AND METHODS--We genotyped 19 single-nucleotide polymorphisms (SNPs) spanning from the 3′ end of the neighboring RPGRIP1L gene to the 5′ flanking region of the FTO gene. We analyzed their associations with obesity (638 case and 1,610 control subjects), type 2 diabetes (759 case and 784 control subjects), and obesity-related traits in nondiabetic subjects. RESULTS--Among the 19 SNPs, the rs9939609 A allele was strongly associated with obesity (P = 7.0 x 10[sup -4]) and BMI (P = 0.0024) in the Chinese population. The odds ratio for obesity was 2.60 (95% CI 1.24-5.46) (P = 0.011) for the AA genotype and 1.32 (1.05-1.66) (P = 0.018) for the AT genotype compared with the TT genotype. Each additional copy of the rs9936609 A allele was associated with a BMI increase of ∼0.37 kg/m[sup 2]. The rs9939609 A allele was substantially less common in the Chinese population than in the European population (12.6 vs. 45%). We did not find significant associations of the 19 SNPs with type 2 diabetes or other obesity-related traits. CONCLUSIONS--Genetic variation in the FTO gene is strongly associated with obesity and BMI in the Chinese population. The risk variant is less common in the Chinese population, but its effect size on BMI is comparable with that in the European population. Diabetes 57:2245-2252, 2008 Obesity is strongly influenced by genetic factors, with an estimated heritability of >60% BMI (1,2). Genetic susceptibility to the common form of obesity appears to be polygenic. Although theoretical analyses emphasized the power of genetic association study in common polygenic diseases, the search for genes conferring the risk of obesity has thus far not been very successful. A few reported associations with genes such as GAD2, ENPP1, and INSIG2 also yielded inconsistent results in replication efforts (3-5). [ABSTRACT FROM AUTHOR]