Abstract
The role of GATA4 in cardiovascular disease remain to be elucidated. We initially sequenced the GATA4 coding regions to identify variants of interest in 250 individuals, and investigated the role of 5 SNPs, rs3729855 (C>T), rs3729856 (A>G), rs1062219 (C>T), rs11785481 (C>T) and rs3203358 (C>G) in predisposing individuals to myocardial infarction (MI) by the real‐time PCR in 3803 individuals, all of Saudi origin. We then tested the impact of congenital heart disease (CHD) by comparing the CHD patients with the rest. The results pointed to a significant association for the rs3729856 (p.S377G) with CHD [Odds ratio(95% Confidence Interval) = [1.48(1.06–2.08); p=0.023], and protective effect for rs3729855 [0.96 (0.42–2.19); p=0.005. In order to rule out the influence of CHD on other relationships, we excluded CHDs from further analyses involving 2713 MI patients and 986 controls. Interestingly, the rs3729856 [1.16(1.01–1.34); p=0.034] also conferred risk for MI, while the rs3729855 [0.68 (0.52–0.89); p=0.005] showed protective properties. Furthermore, both the rs3729856 [1.14(0.99–1.31); p=0.076] and rs3729855 [1.37(1.00–1.88); p=0.052] were also associated with hypertension, but not with type 2 diabetes mellitus. These observations implicate the GATA4 as a susceptibility gene for both MI and CHD.
This work was supported through the Royal Cardiovascular Research Grant of the King Faisal Specialist Hospital and Research Centre