Genetic Variations in the FTO Gene Are Associated with Type 2 Diabetes and Obesity in South Indians (CURES-79)

Aim: The present study investigated the association of six variants-rs9940128, rs7193144, and rs8050136 (in intron 1), rs918031 and rs1588413 (in intron 8), and rs11076023 (3 ' untranslated region)-across three regulatory regions of the fat mass and obesity-associated (FTO) gene with obesity and type 2 diabetes mellitus (T2DM) in a South Indian population.Methods: Unrelated study subjects (n = 1,852; 1,001 normal glucose-tolerant [NGT] controls and 851 cases [T2DM]) were randomly selected from the Chennai Urban Rural Epidemiological Study (CURES). Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism method, and 20% of samples were sequenced to validate the genotypes obtained. Haplotype analysis was also carried out.Results: The three polymorphisms rs9940128 A/G, rs1588413 C/T, and rs11076023 A/T of the FTO gene were associated with T2DM in our study population. The rs8050136 C/A variant was associated with obesity, and its association with T2DM was also mediated through obesity. The rs1588413 C/T variant showed an association with obesity in the total study subjects, but when the NGT subjects alone were analyzed, the association with obesity was lost. The haplotype ACCTCT confers a lower risk of T2DM in this South Indian population.Conclusions: Among South Indians, the rs9940128 A/G, rs11076023 A/T, and rs1588413 C/T variants of the FTO gene were associated with T2DM, whereas the rs8050136 C/A variant was associated with obesity.