Lockette W, Ghosh S, Farrow S, MacKenzie S, Baker S, Miles P, Schork A, Cadaret L
Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Am J Hypertens. 1995 Apr;8(4 Pt 1):390-4. doi: 10.1016/0895-7061(95)00024-j.
alpha 2-Adrenergic receptors are found on presynaptic neurons of the central and peripheral nervous systems, on blood vessels, on platelets, on adipocytes, and in the kidney and pancreas. Activation of these ubiquitous adrenoreceptors results in decreased neuronal norepinephrine release, vasodilation, a fall in blood pressure, platelet aggregation, increased sodium excretion, and decreased insulin release. We hypothesized that defects in alpha 2-adrenergic receptors, or postreceptor defects, could explain the increased prevalence of hypertension in blacks. To test our hypothesis, we first determined whether or not a polymorphism of the alpha 2-adrenergic receptor gene was associated with pathologic elevations in blood pressure in American blacks. Dra-I identified a restriction fragment-length polymorphism (RFLP) of 6.3 and 6.7 kb of the alpha 2-adrenergic receptor gene on chromosome 10 in humans. Of 227 patients studied, 13/107 hypertensive subjects were homozygous for the 6.3-kb allele, whereas only 3/120 normotensive volunteers were homozygotes (P = .008). When analyzed by race, 13/82 black hypertensive subjects were homozygous for the 6.3-kb allele, whereas only 2/59 normotensive blacks were homozygous for the 6.3-kb alleles (P = .02). However, only 1/61 white normotensive and 0/25 white hypertensive subjects were homozygous for the 6.3-kb allele (P = 1.00). Ethnic variation among blacks may explain our findings. Alternatively, a genetic polymorphism in, or near, the alpha 2-adrenergic receptor on chromosome 10 can contribute to the development of hypertension in blacks.
α2-肾上腺素能受体存在于中枢和外周神经系统的突触前神经元上、血管上、血小板上、脂肪细胞上以及肾脏和胰腺中。这些普遍存在的肾上腺素能受体被激活后，会导致神经元去甲肾上腺素释放减少、血管舒张、血压下降、血小板聚集、钠排泄增加以及胰岛素释放减少。我们推测，α2-肾上腺素能受体缺陷或受体后缺陷可能是黑人高血压患病率增加的原因。为了验证我们的假设，我们首先确定α2-肾上腺素能受体基因的多态性是否与美国黑人的病理性血压升高有关。Dra-I识别出人类10号染色体上α2-肾上腺素能受体基因的6.3和6.7 kb限制性片段长度多态性（RFLP）。在研究的227名患者中，107名高血压患者中有13名是6.3 kb等位基因的纯合子，而120名血压正常的志愿者中只有3名是纯合子（P = 0.008）。按种族分析时，82名黑人高血压患者中有13名是6.3 kb等位基因的纯合子，而59名血压正常的黑人中只有2名是6.3 kb等位基因的纯合子（P = 0.02）。然而，61名血压正常的白人中只有1名是6.3 kb等位基因的纯合子，25名白人高血压患者中没有（P = 1.00）。黑人之间的种族差异可能解释了我们的研究结果。或者，10号染色体上α2-肾上腺素能受体内部或附近的基因多态性可能导致黑人高血压的发生。
