IGF2BP2 Genetic Variation and Type 2 Diabetes: A Global Meta-Analysis

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is involved in the stimulation of insulin action. Polymorphisms in the IGF2BP2 gene have been analyzed in numerous studies to assess the type 2 diabetes (T2D) risk attributed to these variants, but results are conflicting. To better understand the effect of rs4402960 polymorphism on T2D risk, we performed a comprehensive meta-analysis that included 35 published studies involving 70,261 cases and 100,567 controls. The relatively infrequent T variant was significantly associated with T2D with a per-allele odds ratio (OR) of 1.14 (95% confidence interval (CI): 1.12-1.16; p<10(-5)). Significant results were also observed for heterozygous (OR=1.17, 95% CI: 1.14-1.20; p<10(-5)) and homozygous (OR=1.23, 95% CI: 1.16-1.30; p<10(-5)) compared with wild type. In the subgroup analysis by ethnicity, significantly increased risks were found in East Asian, Caucasian and Indian populations. However, no significant associations were detected among other ethnicities. In the stratified analysis according to sample size, diagnostic criterion, mean body mass index, and age of cases significantly increased risks for the polymorphism were found in all genetic models. In conclusion, this meta-analysis suggests that rs4402960 polymorphism in IGF2BP2 is associated with elevated T2D risk, but these associations vary in different ethnic populations.