A contribuição dos polimorfismos (SNPs) do FTO e UCP-1 com a obesidade extrema e fatores de risco cardiovascular em indivíduos brasileiros

Abstract

Obesity has become a common human disorder associated with significant morbidity, mortality and adverse effects on quality of life. Several candidate genes have reportedly been associated with obesity, related metabolic disorders and diabetes. Sequence variants in two of the prominent ones, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype and a multiethnic group such as the Brazilian population has not been previously reported. To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk in Brazilian individuals we genotyped SNPs rs9939609 in the FTO and rs6536911, rs22705565 and rs12502572 in the UCP-1 genes from 126 morbidly obese subjects (BMI . 42.9 } 5.6 kg/m2) and 113 normal-weight ethnically matched control (BMI 22.6 } 3.5 kg/m2). Waist circumference, blood pressure, glucose and serum lipids were also measured. Genotyping was performed using TaqMan. SNP Genotyping Assays. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) used for ethnic assignment and the estimatation of the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population. Cases did not differ from controls in the proportions of genomics ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536911 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536911 sample of controls. No other significant associations between any SNP and hypertension, hyperlipidemia and diabetes were noted after correction for BMI and no significant synergistic effect between FTO and UCP-1 SNPs with obesity were noted. Our data are consistent with FTO rs9939609 and UCP-1 rs6536911 common variants as possible contributors to obesity in the Brazilian population.