GNAQ TT(-695/-694)GC Polymorphism Is Associated with Increased Gq Expression, Vascular Reactivity, and Myocardial Injury after Coronary Artery Bypass Surgery

BACKGROUND: Angiotensin II receptor type 1-mediated activation of the α-subunit of the heterotrimeric Gq protein evokes increased vasoconstriction and may promote hypertrophy-induced myocardial damage. The authors recently identified a TT(-695/-694)GC polymorphism in the human Gq promoter, the GC allele being associated with an increased prevalence of cardiac hypertrophy. In this article, the authors tested whether the TT(-695/-694)GC polymorphism is associated with differences in (1) myocardial Gq protein expression, (2) vascular reactivity, and (3) myocardial damage after coronary artery bypass grafting. METHODS: Gq protein expression was measured in right atrial muscle from 55 patients undergoing coronary artery bypass grafting as were skin perfusion changes (n = 18; laser Doppler imaging), saphenous vein ring vascular reactivity (n = 50, organ bath) in response to angiotensin II, and myocardial damage (227 patients undergoing coronary artery bypass grafting), as assessed by postoperative cardiac troponin I concentration. RESULTS: Myocardial Gq expression was greater in GC/GC genotypes (GC/GC vs. TT/TT: 1.27-fold change; P = 0.006). Skin perfusion after intradermal angiotensin II injection decreased only in GC/GC genotypes (P = 0.0002). Saphenous vein rings exposed to increasing angiotensin II concentrations showed an almost doubled maximum contraction in GC/GC compared with individuals with the TT/TT genotype (P = 0.022). In patients undergoing coronary artery bypass grafting, baseline cardiac ejection fraction was different (GC/GC: 55 ± 13%; GC/TT: 54 ± 14%; TT/TT: 48 ± 15%; P = 0.037) and postoperative peak cardiac troponin I was greater in patients with the GC/GC (11.5 ± 13.8 ng/ml) than in patients with the GC/TT (9.2 ± 9.2 ng/ml) or patients with the TT/TT genotype (6.6 ± 4.8 ng/ml, P = 0.015). CONCLUSIONS: The GC/GC genotype of the TT(-695/-694)GC polymorphism is associated with increased Gq protein expression, augmented angiotensin II receptor type 1-related vasoconstriction, and increased myocardial injury after coronary artery bypass grafting, highlighting the impact of Gq genotype variation.