Associations of GATA4 genetic mutations with the risk of congenital heart disease

BACKGROUND GATA4 gene is a cardiac transcriptional factor playing important role in cardiac formation and development. Three GATA4 gene mutations, 99 G>T, 487 C>T, and 354 A>C, have been reported in congenital heart disease (CHD). Therefore, a meta-analysis was performed to explore the associations between 99 G>T, 487 C>T, or 354 A>C mutations and the risk of CHD. METHODS We searched the relevant studies in electronic databases, including ISI Science Citation Index, Embase, PubMed, CNKI, and Wan fang, from January 2006 to March 2016. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the associations between 99 G>T, 487 C>T, or 354 A>C mutations and the risk of CHD. RESULTS A total of 11 studies including 2878 CHD cases and 3339 controls were evaluated. There was no significant association between GATA4 99 G>T (OR = 1.22, 95% CI = 0.74-2.01, P = .43) or 487 C>T (OR = 1.16, 95% CI = 0.48-2.78, P = .74) mutations and the risk of CHD, whereas GATA4 354 A>C (OR = 1.49, 95% CI = 1.15-1.93, P = .003) mutation was significantly associated with CHD risk. Subgroup analysis was further performed for GATA4 99 G>T, 487 C>T, and 354 A>C mutations based on sample size and ethnicity, and no significant association between GATA4 99 G>T or 487 C>T mutations and the risk of CHD was found in all subgroups, whereas GATA4 354 A>C mutation was significantly associated with CHD risk in large-sample-size and Asian subgroups. However, subgroup analysis by types of CHD indicated that there was no significant association between GATA4 354 A>C mutation and the risk of ventricular septal defects. CONCLUSIONS Our findings suggested that GATA4 99 G>T and 487 C>T mutations may not be related to the incidence of CHD. However, GATA4 354 A>C mutation was significantly associated with CHD risk.