FTO gene polymorphisms and obesity risk: a meta-analysis

Abstract

BackgroundThe pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (FTO); however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion.MethodsWe searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR) and their 95% confidence intervals (CI) were estimated using per-allele comparison. Summary ORs were estimated using a random effects model.ResultsWe identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36), rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53), rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38), rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68), and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62). Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with I2 test values ranging from 38.1% to 84.5%.ConclusionsThis meta-analysis suggests that FTO may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

“…In the large meta-analysis of GWAS, thus far performed with 123,865 individuals of European ancestry, the FTO locus was confirmed as one of the 32 variants associated with BMI with p-values \5 9 10 -8 (Speliotes et al 2010;Speakman et al 2011). A significant association between rs9939609 SNP of FTO gene and obesity, with an overall odds ratio (OR) for obesity of 1.31 under per-allele comparison, was reported in another meta-analysis including 111,571 subjects (Peng et al 2011).…”

The Frequencies of Haplotypes of FTO Gene Variants and Their Association with the Distribution of Body Fat in Non-Obese Poles

“…Among those of European ancestry, all identified FTO SNPs significantly associated with obesity (located within the first intron) are part of a highly correlated linkage disequilibrium block. [4][5][6][7].…”

Rola genu podatności na otyłość (FTO) w rozwoju otyłości — przegląd

“…Vimaleswaran et al showed a reduced, but still significant, effect of the rs1121980 polymorphism on both BMI and waist circumference in physically active individuals compared to an inactive group (20,374 European adults) [70]. Similarly, Andearsen et al [11] found an interaction between the FTO rs9939609 genotype and self-reported physical activity on BMI levels in the Inter99 study sample.…”

“…The effect of the variant of FTO on adiposity varies among different populations [20]. In an Asian population, initial studies did not confirm the role of FTO.…”

“…Peng et al [20] meta-analysed 59 case-control studies and identified five polymorphisms (rs993609, rs17817449, rs1421085, rs8050136, rs1121980) associated with obesity in different ethnic groups. However, in some subgroups there was no correlation, for instance for rs993609 with Hispanic and Caucasian or rs8050136 with Asians and Africans.…”