Snapir A, Heinonen P, Tuomainen T P, Alhopuro P, Karvonen M K, Lakka T A, Nyyssönen K, Salonen R, Kauhanen J, Valkonen V P, Pesonen U, Koulu M, Scheinin M, Salonen J T
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
J Am Coll Cardiol. 2001 May;37(6):1516-22. doi: 10.1016/s0735-1097(01)01201-3.
Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases.
alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction.
This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years.
In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population.
The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.
我们的目的是研究α2B - 肾上腺素能受体基因中的插入/缺失（I/D）多态性是否与心血管疾病风险相关。
α2 - 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。α2 - 肾上腺素能受体亚型B在小鼠中介导血管收缩。已显示人类α2B - 肾上腺素能受体基因的一种变体在细胞内酸性基序中编码三个残基的缺失，该变体可导致受体脱敏降低。因此，这种受体变体可能参与与血管收缩增强相关的疾病。
本研究是一项基于人群的前瞻性研究的一部分，该研究调查了芬兰东部一组中年男性心血管疾病的危险因素。912名年龄在46至64岁之间的男性被随访了平均4.5年。
在本研究人群中，192名男性（21%）具有D/D基因型；256名（28%）具有I/I基因型，464名（51%）具有杂合基因型。在调整了其他冠状动脉危险因素的Cox模型中，与携带其他两种基因型之一的男性相比，具有D/D基因型的男性发生急性冠状动脉事件的风险高2.2倍（95%置信区间：1.1至4.4，p = 0.02）（D/D组有15例，I/I组有10例，I/D组有12例）。在本研究人群中，α2B - 肾上腺素能受体基因型与高血压无关。
α2B - 肾上腺素能受体的D/D基因型是急性冠状动脉事件的一种新的遗传危险因素，但不是高血压的遗传危险因素。
