Dhein Stefan, Dohmen Pascal M, Sauer Matthias, Tews Julia, Weickmann Johannes, Funkat Anne-Kathrin, Misfeld Martin, Borger Michael A, Mohr Friedrich W
Department of Cardiac Surgery, Heart Center Leipzig University of Leipzig, Leipzig, Germany.
Department of Cardiac Surgery, European University Oldenburg-Groningen, Oldenburg, Germany.
Med Sci Monit Basic Res. 2017 May 19;23:223-233. doi: 10.12659/msmbr.902820.
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.
背景 关于β-肾上腺素能受体多态性在心血管系统中的作用，一直存在着长期的争论。我们想要阐明β1-肾上腺素能受体多态性是否会影响心脏手术患者术后儿茶酚胺的消耗以及在中间护理单元的住院时间，以及儿茶酚-O-甲基转移酶（COMT）多态性是否会增强或减弱这种影响。材料与方法 我们纳入了116例接受心脏手术的患者（年龄63±1.2岁；女性占34%；体重81±1千克）。我们通过使用荧光共振能量转移的实时聚合酶链反应（PCR-FRET）评估了Arg389Gly和Ser49Gly-β1-肾上腺素能受体（B1AR）多态性以及Val158Met-COMT多态性。术前风险通过欧洲心脏手术风险评估系统（EuroSCORE）进行评估。此外，我们使用电化学高效液相色谱法测量了术前内源性肾上腺素和去甲肾上腺素的血浆浓度。结果 84.6%的患者为Ser49Ser纯合子，52.1%为Arg389Arg B1AR纯合子，32.5%为Val158Val-COMT纯合子，而15.4%的患者表现为Ser49Gly B1AR，38.5%为Arg389Gly-B1AR，35.6%为Val158Met-COMT。我们发现Gly49变异体、Gly389变异体和Val158-COMT变异体与术后较高的去甲肾上腺素消耗有关。所有携带Val158-COMT等位基因的患者术前去甲肾上腺素浓度较高。此外，我们发现两种β1-肾上腺素能受体多态性均与较长的住院时间有关，而这受到COMT多态性的调节。结论 这些数据表明，在心脏手术后的术后阶段所反映的心血管应激增强的情况下，β1-肾上腺素能受体多态性与COMT多态性共同影响去甲肾上腺素的消耗和住院时间。此外，我们得出结论，具有Val158-COMT基因型的患者表现出较高的内源性静息血浆去甲肾上腺素水平。
