Association study of six single nucleotide polymorphisms with obesity in two independent Iberian samples

Abstract

Several BMI associated-loci conferring susceptibility to obesity have been identified. Summarizing all these risk-associated variations into a genetic risk-score (GRS) may improve predictive power and cumulative effect on obesity risk. In this study, we investigate the reproducibility in two independent samples of the association and weighted GRS previously proposed for six SNPs as predictors for obesity susceptibility. A case-control study was performed using one sample comprising 346 unrelated Portuguese children [6–12 years-old; 191 controls and 155 obese], and a second sample comprising 332 unrelated Spanish adults [18–60 years-old; 217 controls and 115 obese]. Polymorphisms located on FTO, TFAP2B, SEC16B, ETV5, and SH2B1 genes were genotyped by allelic discrimination TaqMan assays.After Bonferroni corrections we found nominal significant associations of the rs17817449 FTO polymorphism with BMI (p = 0.023), Z-score (p = 0.009), weight (p = 0.020), and waist circumference (p = 0.022) in the Portuguese children. A nominal association was also observed with risk of obesity (p = 0.027). The same polymorphism was found significantly associated with obesity (p = 0.0005) in Spanish adults. Nominal association with risk of obesity was also found for rs7634510 ETV5 polymorphism (p = 0.011). No further associations were observed for the other polymorphisms. Our results failed to replicate a previously proposed GRS predicting high susceptibility to childhood obesity. Nonetheless, we highlight the role of the rs17817449 FTO polymorphism on obesity in both Portuguese and Spanish samples, as well as the rs7634510 ETV5 polymorphism in adults.