The Impact of Variants in Four Genes: MC4R, FTO, PPARG and PPARGC1A in Overweight and Obesity in a Large Sample of the Brazilian Population.

Obesity and overweight are worldwide public health problems with an evident genetic predisposition that is still poorly understood. In addition, great variability has been described across populations. In this work, we analyzed the association of variants in four genes: PPARG (rs1801282), PPARGC1A (rs8192678), FTO (rs9939609) and MC4R (rs17782313) with overweight and obesity in a large sample of the Brazilian population. The case-control study involved 4084 individuals (1844 with overweight or obesity; and 2240 with normal BMI). Genotyping was performed by quantitative PCR. MC4R rs17782313-C was associated with obesity (OR = 1.27, p = 0.038) and when stratifying by sex associated only in women (OR = 1.36, p = 0.030). FTO rs9939609-A allele was associated with overweight however for women it represented a risk factor (OR = 1.24, p = 0.034) and for men, a protective factor (OR = 0.68, p = 0.033). PPARG was the strongest associated gene, with both overweight and obesity, and this association was also restricted to women (rs1801282-GG OR = 1.46, p = 0.027). The combined effect of the three risk alleles on overweight and obesity had an OR of 1.65 (p = 0.008) and when stratifying by sex again it was significant only in females (OR = 1.95, p = 0.0028). Our findings indicate that the three genes play a significant role in predisposing to overweight and/or obesity in the Brazilian population, reaching together a relatively high impact on these traits. Interestingly our results also suggest a strong sex-specific genetic effect of these variants.