Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute Salt Loading
Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute Salt Loading
复制标题
SLC8A1 基因的遗传变异参与急性盐负荷的血压反应
DOI：
10.1093/ajh/hpx179
复制
发表时间：
2018-04-01
影响因子：
3.2
通讯作者：
Zhang, Ling
中科院分区：
文献类型：
--
作者：
Liu, Kuo;Liu, Zheng;Zhang, Ling
背景
血压盐敏感性（SSBP）会增加心血管并发症的风险，在中国人群中SSBP的遗传力约为50%。然而，识别参与血压对急性钠负荷和利尿收缩反应的基因的研究仍然有限。
方法
我们的研究共招募了 342 名来自北京的原发性高血压患者。对每个个体进行改良的沙利文急性口服盐水负荷和利尿收缩试验。通过问卷调查获得病史和生活方式危险因素。使用广义线性模型来检查 29 个单核苷酸多态性 (SNP) 与 SSBP 的关联，并使用错误发现率 (FDR) 来校正多重测试的 P 值。
结果
在急性钠负荷过程中，调整年龄和24小时尿钠浓度后，CYP11B2、PRKG1、SLC8A1基因中的SNP在加性和隐性模型中与收缩压（SBP）升高显着相关； CYP4A11、PRKG1、SLC8A1 和 ADRB2 基因中的 SNP 与舒张压 (DBP) 升高显着相关。在利尿收缩过程中，CLCNKA、eNOS、PRKG1基因的SNP与SBP和DBP降低相关。经过FDR校正后，SLC8A1基因中的rs434082仍然与盐负荷期间血压升高显着相关。在加法模型中，调整年龄和 24 小时尿钠浓度后，A 等位基因使 DBP 增加 2.8 mm Hg (FDR_q = 0.029)，MAP 增加 3.1 mm Hg (FDR_q = 0.029)。
结论
SLC8A1基因可能与中国汉族人群急性钠负荷过程中的血压变化有关。
BACKGROUND
Salt sensitivity of blood pressure (SSBP) increases the risk of cardiovascular complications, and the heritability of SSBP is about 50% in Chinese population. However, studies identifying genes involved in BP responses to acute sodium loading and diuresis shrinkage are still limited.
METHOD
A total of 342 essential hypertensives from Beijing were recruited in our study. A modified Sullivan's acute oral saline load and diuresis shrinkage test was conducted to each individual. Medical history and lifestyle risk factors were obtained by questionnaire. Generalized linear model was used to examine the associations of 29 single-nucleotide polymorphisms (SNPs) with SSBP and false discovery rate (FDR) was used to correct P values for multiple testing.
RESULTS
In the process of acute sodium loading, after adjusting for age and 24-hour urinary sodium concentration, SNPs in CYP11B2, PRKG1, SLC8A1 genes were significantly associated with systolic BP (SBP) rising in the additive and recessive model; SNPs in CYP4A11, PRKG1, SLC8A1, and ADRB2 genes were significantly associated with diastolic BP (DBP) rising. In the process of diuresis shrinkage, SNPs of CLCNKA, eNOS, PRKG1 gene were associated with SBP and DBP decreasing. After FDR correction, rs434082 in SLC8A1 gene was still significantly associated with blood pressure rising during salt load. In the additive model, A allele increased DBP of 2.8 mm Hg (FDR_q = 0.029) and MAP of 3.1 mm Hg (FDR_q = 0.029) after adjusting for age and 24-hour urinary sodium concentration.
CONCLUSION
SLC8A1 gene may contribute to BP change in the process of acute sodium loading in a Han Chinese population.