Abstract
BackgroundObesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported.MethodsTo assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565 and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m2, mean ± SE) and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m2, mean ± SE). Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population.ResultsCases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536991 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. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1) in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery.ConclusionOur data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.
Highlights
Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life
The genetic architecture of the fat mass and obesity-associated (FTO) locus has not been examined in great detail in these populations evidence is emerging that rs9939609 might be in tight linkage disequilibrium with a casual variant in populations of European descendent
Taken together we found evidence that rs9939609 in the FTO and rs6536991 in the UCP-1 gene increased the risk of obesity but not obesity related phenotypes in the Brazilian population studied
Summary
Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Three independent genomewide (GWAS) studies reported significant association between obesity (determined by BMI) and common genetic variants in the fat mass and obesity-associated (FTO) gene including the SNP rs9939609 [8,9,10]. This association was replicated in genetically heterogeneous populations of Caucasians and Asians [11,12,13,14], but discordant results have been observed in African populations [15,16,17]. The minor allele frequency in these populations is less than half of that reported for populations of European descent and the patterns of linkage disequilibrium are distinct
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