• Ulrich H Frey, Stefanie Klenke, Anna Mitchell, Tim Knüfermann, Heinz Jakob, Matthias Thielmann, Winfried Siffert, and Jürgen Peters.
• From Klinik für Anästhesiologie und Intensivmedizin (U.H.F., S.K., T.K., J.P.), Die Blutdruck Praxis, Dorsten (A.M.), Klinik für Thorax- und kardiovaskuläre Chirurgie (H.J., M.T.), and Institut für Pharmakogenetik (W.S.), Universität Duisburg-Essen, Essen; and Universitätsklinikum Essen (U.H.F., S.K., T.K., J.P., H.J., M.T.), Essen, Germany.
• Anesthesiology. 2017 Jul 1; 127 (1): 70-77.

BackgroundAngiotensin 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.MethodsGq 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.ResultsMyocardial Gq expression was greater in GC/GC genotypes (GC/GC vs.Tt/Tt1.27-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).ConclusionsThe 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.

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