Aims and hypothesis
Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations
are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not
seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune.
Methods
We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals
from Mysore, South India.
Results
We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13–1.40;
p = 3 × 10−5). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01–0.10) than the
previously reported effect in Europeans (0.10 SDs; 95% CI 0.09–0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per
allele for type 2 diabetes 1.21; 95% CI 1.06–1.37; p = 4.0 × 10−3), and also for waist circumference and other anthropometric variables.
Conclusions
Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely
mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body
size with type 2 diabetes.
Keywords Body mass index - Ethnicity -
FTO
- Polymorphisms - Type 2 diabetes mellitus
C. S. Janipalli, S. Bhaskar, S. R. Kulkarni and R. M. Freathy contributed equally to this study.