Genetic variants in the renin-angiotensin-aldosterone system and blood pressure responses to potassium intake
Genetic variants in the renin-angiotensin-aldosterone system and blood pressure responses to potassium intake
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DOI：
10.1097/hjh.0b013e32834a4d1f
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发表时间：
2011-09-01
影响因子：
4.9
通讯作者：
Whelton, Paul K.
中科院分区：
文献类型：
--
作者：
He, Jiang;Gu, Dongfeng;Whelton, Paul K.
目的观察性流行病学研究和临床试验证明，膳食钾摄入量可降低血压。我们研究了肾素-血管紧张素-醛固酮系统的遗传变异与血压对钾干预反应的关系。方法对1906名中国北部农村受试者进行7d高钠后7d高钠+60 mmo1/d补钾喂养研究。结果肾素-血管紧张素-醛固酮系统11个候选基因的181个单核苷酸多态(SNPs)、血管紧张素Ⅱ1型受体(AGTR1)、羟基类固醇(11-β)脱氢酶1(HSD11B1)和羟基类固醇(11-β)脱氢酶2(HSD11B2)基因的多个单核苷酸多态性(SNPs)与血压对钾干预的反应显著相关。例如，NR3C2基因N554S错义突变(Rs5527)的G等位基因数与钾干预的SBP反应显著相关，A/A和A/G的平均[95%可信区间(CI)]分别为-3.33(-3.65~-3.02)和-5.47(-6.64~-4.29)(P值=0.0004)。此外，AGTR1基因A1166C变异(Rs5186)的C等位基因数目与钾干预的SBP反应显著负相关；A/A、A/C和CC的平均反应(95%CI)分别为-3.55(-3.87~-3.24)、-2.45(-3.27~-1.62)和3.25(-5.73~12.23)(P=0.003)。结论肾素-血管紧张素-醛固酮系统的遗传变异可能在决定个体对膳食钾摄入量的血压反应中起重要作用。J Hyperten 29：1719-1730(C)2011年沃尔特斯·克鲁沃健康垂直酒吧Lippincott Williams&Wilkins。
Objective Observational epidemiologic studies and clinical trials have documented that dietary potassium intake lowers blood pressure (BP). We examined the association between genetic variants in the renin-angiotensinaldosterone system and BP responses to potassium intervention.Methods A 7-day high-sodium followed by a 7-day high-sodium plus 60 mmol/day potassium-supplementation feeding study was conducted among 1906 participants from rural northern China. Nine BP measurements were obtained at each intervention phase using a random-zero sphygmomanometer and 181 single-nucleotide polymorphisms (SNPs) in 11 candidate genes of the renin-angiotensin-aldosterone system were used for analyses.Results Several SNPs in nuclear receptor subfamily 3, group C, member 2 (NR3C2), angiotensin II type 1 receptor (AGTR1), hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1), and hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2) genes were significantly associated with BP responses to potassium intervention. For example, the number of G alleles of the N554S missense mutation (rs5527) of NR3C2 was significantly associated with greater SBP responses to potassium intervention; mean [95% confidence interval (CI)] responses (mmHg) were -3.33 (-3.65 to -3.02) for genotype A/A and -5.47 (-6.64 to -4.29) for A/G, respectively (P value = 0.0004). In addition, the number of C alleles of the A1166C variant (rs5186) in AGTR1 was significantly and inversely associated with SBP responses to potassium intervention; mean (95% CI) responses were -3.55 (-3.87 to -3.24) for genotype A/A, -2.45 (-3.27 to -1.62) for A/C, and 3.25 (-5.73 to 12.23) for CC (P value = 0.003).Conclusion These novel findings indicated that genetic variants in the renin-angiotensin-aldosterone system may play an important role in determining an individual's BP responses to dietary potassium intake. J Hypertens 29:1719-1730 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.