Associations of NKX2-5 Genetic Polymorphisms with the Risk of Congenital Heart Disease: A Meta-analysis

Abstract

The NKX2-5 gene is a vital regulator of cardiac formation and development. Recently, the roles of NKX2-5 63A>G polymorphism and 606G>C polymorphism in congenital heart disease (CHD) have been extensively studied, with conflicting results. The aim of the present study was to better elucidate the associations between NKX2-5 genetic polymorphisms and CHD risk through a meta-analysis. Eligible articles were searched in PubMed, MEDLINE, EMBASE, Google Scholar and CNKI up to December 2015. Odds ratios (ORs) and 95 % confidence intervals were used to detect any potential associations between NKX2-5 genetic polymorphisms and CHD risk. Heterogeneity between studies was assessed with Q test and I (2) statistic. Subgroup analysis and sensitivity analysis were performed to test the reliability and stability of the results, and funnel plots were applied to estimate publication bias. A total of 13 case-control studies including 2245 CHD patients and 1953 healthy controls were analyzed. The overall meta-analysis results showed that NKX2-5 63A>G polymorphism and 606G>C polymorphism were not significantly associated with CHD risk. Subgroup analysis was further performed for NKX2-5 63A>G polymorphism based on types of CHD and ethnicity of study population, and similar negative results were found in all subgroups. Our findings suggested that NKX2-5 63A>G polymorphism and 606G>C polymorphism may not be implicated in the pathogenesis of CHD.

Keywords: Congenital heart disease (CHD); Genetic polymorphisms; Meta-analysis; NKX2-5.