An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference

Abstract

Aims-A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use metaanalyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians.Methods-We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged ≥ 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined Results-In the 4411 Pakistani individuals from this study, the age-, sex-and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24-0.67) kg/m 2 per A-allele (P = 3.0× 10 −5 ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P = 0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95% CI) 1.18 (1.07-1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14-1.31); P = 1.07× 10 −8 ] even after adjusting for BMI [1.18 (95% CI 1.10-1.27); P = 1.02× 10 −5 ] or waist circumference [1.18 (95% CI 1.10-1.27); P = 3.97× 10 −5 ].Conclusions-The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

Multiple genetic variants explain measurable variance in type 2 diabetes-related traits in Pakistanis

“…Thus, with regard to the FTO variant known to be associated with BMI in Europeans, we have recently shown that its association with type 2 diabetes differs between Europeans and South Asians, probably because BMI is a poorer surrogate of adiposity in South Asians [14].…”

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

“…The first surge of T2DM GWA identified among others the fat mass and obesity-associated gene (FTO), which is the strongest obesity genetic risk factor reported so far 6,7 . It has been shown to confer susceptibility to T2DM in the presence 8,9 and absence of obesity 10,11 . The most widely studied SNP of the ENPP1, K121Q (rs1044498), has produced conflicting results in relation to T2DM susceptibility [12][13][14] .…”

Rola genu podatności na otyłość (FTO) w rozwoju otyłości — przegląd

“…The authors concluded that Asians have generally lower BMI than Europeans and are more susceptible to T2D probably due to higher visceral obesity [47]. Other studies also reported that the association between FTO loci and T2D remains significant after a BMI adjustment [48,49], but some showed BMI-dependent relation with T2D [23,50]. A meta-analysis from Li et al [26], combining data PRACE POGLĄDOWE of 96,551 Asians from 32 populations, confirmed the association of FTO variance and T2D, which was not abolished after an adjustment of BMI.…”