Abstract
Obesity is highly heritable, but the specific genes influencing obesity related traits are largely unknown. Fibroblast growth factor 2 (FGF2) could influence adipocyte differentiation. However, the association of FGF2 polymorphisms and obesity remains unclear. This study aimed to investigate the associations of both the plasma FGF2 levels and SNPs in FGF2 gene with obesity phenotypes in Han Chinese populations. Plasma FGF2 levels were measured and subjected to association analyses in 62 subjects. Eleven SNPs in FGF2 were genotyped and tested for associations in a discovery sample of 1,300 subjects. SNPs significantly associated with obesity were subjected to replication in another independent sample of 1,035 subjects. We found that plasma FGF2 levels were positively correlated with fat mass (P = 0.010). Association analyses in the discovery sample identified three SNPs (rs1449683, rs167428, rs308442) significantly associated with fat mass after multiple testing adjustments (P < 0.0045). Subsequent replication study successfully validated one SNP (rs167428) associated with fat mass (Pcombine = 3.46 × 10−5). eQTL analyses revealed that SNPs associated with obesity also affected FGF2 expression. Our findings suggested that high plasma FGF2 level correlated with increased risk of obesity, and FGF2 gene polymorphisms could affect individual variances of obesity in Han Chinese population.
Highlights
Obesity is a major worldwide health problem associated with increased risk of type 2 diabetes, heart diseases, and several forms of cancer[1]
Meta-analysis was performed with effect size estimates weighted by the inverse of the corresponding standard errors. aA1 represents the minor allele. bWHRadjBMI and HIPadjBMI association P values are from the GIANT Consortium of 210,088 European individuals. cP values are from the DIAGRAM
Given the biological function of Fibroblast growth factor 2 (FGF2) protein involved in adipocytes, it is reasonable to hypothesize that FGF2 could influence adipose-related trait
Summary
Obesity is a major worldwide health problem associated with increased risk of type 2 diabetes, heart diseases, and several forms of cancer[1]. The identified loci together only account for a small proportion of the genetic predisposition (< 10%) to obesity, suggesting that many more associated variants remain to be discovered. Previous functional studies revealed a close relationship between FGF2 and adipocytes. Only one study indicated a negative correlation between serum FGF2 levels and BMI in 30 Japanese overweight men[11]. Shungin et al has reported a SNP (rs303084) near FGF2 as a new loci associated with waist-hip ratio adjusting for BMI (WHRadjBMI)[12], as the only genetic association evidence to reveal the relationship of FGF2 with obesity. The aims of this study were as follows: 1) to evaluate the associations of plasma FGF2 levels with obese status and 2) to investigate the relationship of SNPs in FGF2 with obesity related traits in Han Chinese populations
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