Perioperative Medicine  |   July 2017
GNAQ TT(-695/-694)GC Polymorphism Is Associated with Increased Gq Expression, Vascular Reactivity, and Myocardial Injury after Coronary Artery Bypass Surgery
Author Notes
  • 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.
  • Submitted for publication November 8, 2016. Accepted for publication March 13, 2017.
    Submitted for publication November 8, 2016. Accepted for publication March 13, 2017.×
  • Address correspondence to Prof. Dr. med. Frey: Klinik für Anästhesiologie and Intensivmedizin, Hufelandstr. 55, Universitätsklinikum Essen, D-45122 Essen, Germany. ulrich.frey@uk-essen.de. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Clinical Science / Cardiovascular Anesthesia / Trauma / Burn Care
Perioperative Medicine   |   July 2017
GNAQ TT(-695/-694)GC Polymorphism Is Associated with Increased Gq Expression, Vascular Reactivity, and Myocardial Injury after Coronary Artery Bypass Surgery
Anesthesiology 7 2017, Vol.127, 70-77. doi:10.1097/ALN.0000000000001642
Anesthesiology 7 2017, Vol.127, 70-77. doi:10.1097/ALN.0000000000001642
Abstract

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.