Department of Medicine, Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK.
Am J Hypertens. 2019 Apr 22;32(5):447-451. doi: 10.1093/ajh/hpz019.
Activation of beta-1 adrenoreceptor (β1-AR) in the kidney releases renin that plays a major role in the maintenance of blood pressure. Genetic variation in β1-AR could therefore alter the physiological and clinical effects of this hormone. We tested this hypothesis in patients from a primary care cohort being screened for primary hyperaldosteronism (n = 467).
Demographic and hemodynamic data were measured and plasma renin was determined by a standard immunoassay. Subjects were genotyped for the 2 common single-nucleotide polymorphisms Arg389Gly (rs1801253) and Ser49Gly (rs1801252), and thus the 4 possible haplotypes in β1-AR gene.
In patients being screened for hyperaldosteronism, plasma renin was significantly elevated in Ser49 homozygotes (49SS) compared with Gly49 (49G) allele carriers (0.307 ± 0.03 vs. 0.164 ± 0.05; P = 0.01). However, this did not translate into differences in either blood pressure or heart rate. On the other hand, the Arg389Gly polymorphism did not affect either plasma renin or blood pressure in this group. There was also no evidence that the 2 loci were linked in this group of patients.
These data suggest that in this cohort the Ser49 variant of the Ser49Gly β1-AR gene polymorphism associates with higher renin levels. However, these common β1-AR gene polymorphisms do not affect blood pressure in the same cohort.
肾脏中β1 肾上腺素能受体(β1-AR)的激活会释放肾素,肾素在维持血压方面起着重要作用。因此,β1-AR 的遗传变异可能会改变这种激素的生理和临床作用。我们在原发性醛固酮增多症(n = 467)筛查的初级保健队列患者中对此假说进行了检验。
测量人口统计学和血液动力学数据,并通过标准免疫测定法测定血浆肾素。对β1-AR 基因的 2 个常见单核苷酸多态性 Arg389Gly(rs1801253)和 Ser49Gly(rs1801252)进行基因分型,从而确定β1-AR 基因中的 4 种可能的单倍型。
在筛查醛固酮增多症的患者中,Ser49 纯合子(49SS)的血浆肾素水平明显高于 Gly49(49G)等位基因携带者(0.307 ± 0.03 比 0.164 ± 0.05;P = 0.01)。然而,这并未转化为血压或心率的差异。另一方面,该多态性在该组患者中也不会影响血浆肾素或血压。在该组患者中,也没有证据表明这 2 个位点存在连锁。
这些数据表明,在该队列中,Ser49Gly β1-AR 基因多态性的 Ser49 变体与较高的肾素水平相关。然而,这些常见的β1-AR 基因多态性不会影响同一队列的血压。