Association of the ENPP1 K121Q polymorphism with susceptibility to type 2 diabetes in different populations: evidence based on 40 studies

The K121Q gene polymorphism of ectoenzyme nucleotide pyrophosphate phosphodiesterase 1(ENPP1) has been widely investigated, however, results have been somewhat conflicting. The aim of this meta-analysis was to establish a precise estimation of the association between ENPP1 gene polymorphisms and type 2 diabetes (T2D). A literature search in PubMed, Embase, Cochrane Library and China Biology Medicine (CBM) databases was conducted on publications published prior to November 21(st), 2013. The combined odds ratio (OR) with 95% confidence intervals (95% CI) was calculated to estimate the strength of the association using a random-effects/fixed-effects model. Statistical analyses were performed using the STATA 11.0 software. For the overall population, there was a significant association between ENPP1 gene polymorphisms and T2D when comparing the Q allele versus K allele (OR = 1.29, 95% CI 1.16-1.44, p = 0.000). Considering diverse ethnic groups, effect sizes were consistent for patients of Caucasian and Asian descent (OR = 1.20, 95% CI = 1.08-1.33 and OR = 1.47, 95% CI = 1.15-1.89, respectively); however, effect size was not consistent for those of African descent. Under other models of inheritance, significant associations were also observed. Sensitivity analyses did not leading to differing he results. In summary, the Q allele of the ENPP1 K121Q gene may contribute to the susceptibility for T2D in Caucasians and Asians.