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19 May 2017 : Original article  

Effects of β-Adrenoceptor and Catechol-O-Methyl-Transferase (COMT) Polymorphism on Postoperative Outcome in Cardiac Surgery Patients

Stefan Dhein1ABCDEFG, Pascal M. Dohmen123ABCDEFG*, Matthias Sauer1BCDE, Julia Tews1BC, Johannes Weickmann1BC, Anne-Kathrin Funkat1ABCD, Martin Misfeld1DEF, Michael A. Borger1CDE, Friedrich W. Mohr1ABE

DOI: 10.12659/MSMBR.902820

Med Sci Monit Basic Res 2017; 23:223-233

Abstract

BACKGROUND: There is a long-standing debate about the role of beta-adrenoceptor polymorphisms in the cardiovascular system. We wanted to elucidate whether β1-adrenoceptor-polymorphisms affects the postoperative catecholamine consumption and the length of intermediate care unit stay in patients undergoing cardiac surgery, and whether this might be enhanced or attenuated by catechol-O-methyl-transferase (COMT) polymorphism.

MATERIAL AND METHODS: We included 116 patients (63±1.2 years; 34% females; 81±1 kg) undergoing cardiac surgery. We assessed Arg389Gly and Ser49Gly-β1-adrenoceptor (B1AR) polymorphism together with Val158Met-COMT polymorphism by real-time PCR using fluorescence resonance energy transfer (PCR-FRET). The preoperative risk was assessed by EuroSCORE. In addition, we measured the endogenous preoperative epinephrine and norepinephrine plasma concentrations using an electrochemical HPLC method.

RESULTS: 84.6% were homozygous for Ser49Ser, 52.1% homozygous for Arg389Arg B1AR, and 32.5% for Val158Val-COMT, while 15.4% showed Ser49Gly B1AR, 38.5% Arg389Gly-B1AR, and 35.6% Val158Met-COMT. We found that the Gly49-variant, the Gly389-variant, and the Val158-COMT-variant were associated with higher postoperative norepinephrine consumption. All patients carrying the Val158-COMT allele exhibited higher preoperative norepinephrine concentrations. Moreover, we found that both β1-adrenoceptor polymorphisms were associated with a longer stay in hospital, which was modulated by the COMT polymorphism.

CONCLUSIONS: These data show that the β1-adrenoceptor polymorphisms, together with the COMT polymorphism, affect norepinephrine consumption and stay in hospital in a situation of enhanced cardiovascular stress, reflected here by the postoperative period after cardiac surgery. Moreover, we conclude that patients with the Val158-COMT genotype exhibit higher endogenous resting plasma norepinephrine levels.

Keywords: Postoperative Care, Receptors, Adrenergic, beta-1, Thoracic Surgery

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416