Laukkanen Jari A, Mäkikallio Timo H, Kauhanen Jussi, Kurl Sudhir
Research Institute of Public Health, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland.
Am Heart J. 2009 Oct;158(4):615-21. doi: 10.1016/j.ahj.2009.07.023.
Adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. A deletion variant of the human alpha(2B)-adrenoreseptor of glutamic acid residues has been associated with impaired receptor desensitization. This receptor variant could, therefore, be involved in cardiovascular diseases associated with enhanced vasoconstriction. Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha(2B)-adrenoceptor gene is associated with the risk for sudden cardiac death.
This was a prospective population-based study investigating risk factors for cardiovascular diseases in middle-aged men from 42 to 60 years from eastern Finland. The study is based on 1,606 men with complete data on DNA observed for an average time of 17 years.
In this study population, 338 men (21%) had the D/D genotype, 467 (29%) had the I/I genotype, and 801 (50%) had a heterozygous genotype. There were 76 sudden cardiac deaths during follow-up (0.81 deaths/1,000 persons per year). In a Cox model adjusting for other coronary risk factors (age, systolic blood pressure, smoking, diabetes, serum low-density lipoprotein and high-density lipoprotein cholesterol, body mass index, and exercise-induced myocardial ischemia), men with the D/D or I/D genotype had 1.97 times (95% CI 1.08-3.59, P = .026) higher risk to experience sudden cardiac death (20 events for D/D genotype, 13 events for I/I genotype, and 43 events for I/D genotype) compared with men carrying the I/I genotype. In addition, the alpha(2B)-adrenoceptor D/D genotype was associated with the risk of coronary heart disease death and acute coronary events, after adjusting for risk factors.
The genetic polymorphism of the alpha(2B)-adrenoreceptor is genetic risk predictor for sudden cardiac death.
肾上腺素能受体介导血管平滑肌收缩并在人体中诱导冠状动脉收缩。人类α(2B)-肾上腺素能受体谷氨酸残基的缺失变异与受体脱敏受损有关。因此，这种受体变异可能与血管收缩增强相关的心血管疾病有关。我们的目的是研究α(2B)-肾上腺素能受体基因中的插入/缺失（I/D）多态性是否与心源性猝死风险相关。
这是一项基于人群的前瞻性研究，调查了芬兰东部42至60岁中年男性的心血管疾病危险因素。该研究基于1606名男性，他们拥有完整的DNA数据，平均观察时间为17年。
在该研究人群中，338名男性（21%）具有D/D基因型，467名（29%）具有I/I基因型，801名（50%）具有杂合基因型。随访期间有76例心源性猝死（每年0.81例死亡/1000人）。在调整了其他冠状动脉危险因素（年龄、收缩压、吸烟、糖尿病、血清低密度脂蛋白和高密度脂蛋白胆固醇、体重指数以及运动诱发的心肌缺血）的Cox模型中，与携带I/I基因型的男性相比，具有D/D或I/D基因型的男性发生心源性猝死的风险高1.97倍（95%CI 1.08 - 3.59，P = 0.026）（D/D基因型20例事件，I/I基因型13例事件，I/D基因型43例事件）。此外，在调整危险因素后，α(2B)-肾上腺素能受体D/D基因型与冠心病死亡风险和急性冠状动脉事件相关。
α(2B)-肾上腺素能受体的基因多态性是心源性猝死的遗传风险预测指标。
