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.

肥胖和超重是世界范围内的公共卫生问题，具有明显的遗传倾向，但仍知之甚少。此外，已经描述了跨人群的巨大差异。在这项工作中，我们在巴西人口的大样本中分析了四个基因中的变异：PPARG (rs1801282)、PPARGC1A (rs8192678)、FTO (rs9939609) 和MC4R (rs17782313) 与超重和肥胖的关系。病例对照研究涉及 4084 人（1844 人超重或肥胖；2240 人 BMI 正常）。通过定量PCR进行基因分型。MC4R rs17782313-C 与肥胖相关（OR = 1.27，p = 0.038）和仅在女性中按性别分层时（OR = 1.36，p  = 0.030）。FTO rs9939609-A 等位基因与超重相关，但对于女性来说，它代表一个风险因素（OR = 1.24，p  = 0.034），而对于男性来说，它是一个保护因素（OR = 0.68，p  = 0.033）。PPARG是最强的相关基因，与超重和肥胖都有关联，而且这种关联也仅限于女性（rs1801282-GG OR = 1.46，p  = 0.027）。三个风险等位基因对超重和肥胖的综合影响的 OR 为 1.65（p  = 0.008），当再次按性别分层时，仅在女性中显着（OR = 1.95，p = 0.0028）。我们的研究结果表明，这三个基因在巴西人口易患超重和/或肥胖方面发挥着重要作用，共同对这些特征产生了相对较高的影响。有趣的是，我们的结果还表明这些变体具有强烈的性别特异性遗传效应。