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Background  NKX2-5 is a transcriptional factor, which plays an important role in heart formation and development. Two genetic variants in the coding region of  NKX2-5,  63A>G (rs2277923) and 606G>C (rs3729753), have been investigated in the risk of congenital heart disease (CHD), although with inconsistent results. Thus, a meta-analysis was performed to clarify the associations between the two variants and CHD risk in the Chinese population.    Methods and Results  Relevant studies were identified by searching PubMed, ISI Web of Science and CNKI databases and by reviewing the reference lists of retrieved articles. Then, the data from eligible studies were combined in an allelic model. A total of 7 and 4 studies were ultimately included for 63A>G and 606G>C, respectively. The results of overall meta-analyses showed that significant association was detected for 63A>G (OR = 1.26, 95% CI = 1.02–1.56,  P   heterogeneity  = 0.009,  I   2  = 65.1%), but not for 606G>C (OR = 1.22, 95% CI = 0.75–1.96,  P   heterogeneity  = 0.412,  I   2  = 0.0%). Regarding 63A>G variant, positive results were also obtained in the subgroups of atrial septal defect and large-sample-size study. Besides, the sensitivity analysis indicated that significant association was still detected after deletion of the individual studies with positive result and striking heterogeneity.    Conclusion  Our results revealed that the 63A>G variant in  NKX2-5 , but not the 606G>C, may contribute to CHD risk for Chinese.

Associations between Two Genetic Variants in NKX2-5 and Risk of Congenital Heart Disease in Chinese Population: A Meta-Analysis