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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。

Genetic susceptibility to salt-sensitive hypertension in a Han Chinese population: a validation study of candidate genes.

机构信息

Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.

出版信息

Hypertens Res. 2017 Oct 5;40(10):876-884. doi: 10.1038/hr.2017.57. Epub 2017 Apr 27.

Abstract

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.

摘要

盐敏感性高血压是一种与遗传因素相关的复杂疾病。本研究旨在探讨汉族人群中 29 个候选单核苷酸多态性与盐敏感性高血压的相关性。共纳入 63 例盐敏感性高血压患者和 279 例盐抵抗性高血压患者。采用改良的 Sullivan 急性口服盐水负荷和利尿收缩试验检测血压盐敏感性。通过问卷获得生活方式危险因素。使用 Sequenom Mass ARRAY 平台对 29 个候选单核苷酸多态性进行基因分型,采用累积遗传风险评分评估联合遗传效应。CYP11B2、PRKG1、ADRB2、FGF5、SLC8A1 和 BCAT1 基因中 8 种基因型和 5 种等位基因的频率在盐敏感性高血压组和盐抵抗性高血压组之间差异有统计学意义。多因素 logistic 回归分析调整年龄和性别后,携带 PRKG1 基因 rs7897633-A、SLC8A1 基因 rs434082-A 和 ADRB2 基因 rs1042714-G 风险等位基因的个体发生盐敏感性高血压的风险分别增加 1.83 倍、2.84 倍和 2.40 倍。采用累积遗传风险评分的联合风险等位基因分析显示,携带 1 个风险等位基因的个体发生盐敏感性高血压的风险增加 2.30 倍,携带 2-4 个风险等位基因的个体发生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,PRKG1 基因 rs7897633-A、SLC8A1 基因 rs434082-A 和 ADRB2 基因 rs1042714-G 与盐敏感性高血压显著相关。来自不同通路的单核苷酸多态性的联合效应导致盐敏感性高血压的高风险。

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