Genetic susceptibility to salt-sensitive hypertension in a Han Chinese population: a validation study of candidate genes
Genetic susceptibility to salt-sensitive hypertension in a Han Chinese population: a validation study of candidate genes
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中国汉族人群盐敏感性高血压的遗传易感性：候选基因的验证研究
DOI：
10.1038/hr.2017.57
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发表时间：
2017-10-01
影响因子：
5.4
通讯作者：
Zhang, Ling
中科院分区：
文献类型：
--
作者：
Liu, Zheng;Qi, Han;Zhang, Ling
盐敏感性高血压是一种与遗传因素有关的复杂疾病。本研究旨在确定29个单核苷酸多态性与中国汉族人群盐敏感性高血压之间的关联。招募了63名盐敏感性高血压患者和279名盐抵抗性高血压对照者。采用改良Sullivan急性口服盐负荷和利尿收缩试验检测血压盐敏感性。通过调查问卷获得生活方式危险因素。我们使用Sequenom Mass ARRAY Platform对29个候选单核苷酸多态性进行基因分型，并使用累积遗传风险评分来评估联合遗传效应。CYP 11B 2、PRKG 1、ADRB 2、FGF 5、SLC 8A 1和BCAT 1基因8种基因型和5种等位基因频率在盐敏感组和盐抵抗组间差异有统计学意义。校正年龄和性别后的多元logistic回归分析显示，携带rs7897633-A（PRKG 1）、rs 434082-A（SLC 8A 1）和rs 1042714-G（ADRB 2）风险等位基因的受试者患盐敏感性高血压的风险分别增加1.83、2.84和2.40倍。使用累积遗传风险评分进行的联合风险等位基因分析显示，携带一种风险的受试者患盐敏感性高血压的风险增加2.30倍，携带2-4种风险的受试者患盐敏感性高血压的风险增加3.32倍。在29个候选单核苷酸多态性中，PRKG 1的rs7897633-A、SLC 8A 1的rs 434082-A和ADRB 2的rs 1042714-G与盐敏感性高血压显著相关。来自不同途径的单核苷酸多态性的联合作用导致盐敏感性高血压的高风险。
Salt-sensitive hypertension is a complex disease associated with genetic factors. This study aimed to identify the association between 29 candidate single-nucleotide polymorphisms and salt-sensitive hypertension in a Han Chinese population. Sixty-three participants with salt-sensitive hypertension and 279 controls with salt-resistant hypertension were recruited. A modified Sullivan's acute oral saline load and diuresis shrinkage test was used to detect blood pressure salt sensitivity. Lifestyle risk factors were obtained via a questionnaire. We used the Sequenom Mass ARRAY Platform to genotype the 29 candidate single-nucleotide polymorphisms, and the cumulative genetic risk score was used to evaluate the joint genetic effect. The frequencies of eight genotypes and five alleles in CYP11B2, PRKG1, ADRB2, FGF5, SLC8A1 and BCAT1 genes differed significantly between the salt-sensitive and salt-resistant hypertension groups. Multiple logistic regression adjusted for age and sex showed that subjects carrying rs7897633-A (PRKG1), rs434082-A (SLC8A1) and rs1042714-G (ADRB2) risk alleles had 1.83-, 2.84-and 2.40-fold increased risk for salt-sensitive hypertension, respectively. Combined risk allele analysis using the cumulative genetic risk score showed that subjects carrying one risk had 2.30-fold increased risk, and those carrying 2–4 risks had 3.32-fold increased risk for salt-sensitive hypertension. Among 29 candidate single-nucleotide polymorphisms, rs7897633-A in PRKG1, rs434082-A in SLC8A1 and rs1042714-G in ADRB2 were significantly associated with salt-sensitive hypertension. A joint effect of single-nucleotide polymorphisms from different pathways contributed to a high risk of salt-sensitive hypertension.