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SLC8A1 基因遗传变异与急性盐负荷后血压反应的关系。

Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute Salt Loading.

机构信息

Department of Epidemiology and Health statistics, School of Public Health, Capital Medical University, Beijing, People's Republic of China.

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

出版信息

Am J Hypertens. 2018 Mar 10;31(4):415-421. doi: 10.1093/ajh/hpx179.

Abstract

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.

摘要

背景

血压对盐的敏感性(SSBP)增加了心血管并发症的风险,而中国人群 SSBP 的遗传率约为 50%。然而,鉴定与急性钠负荷和利尿收缩时血压反应相关的基因的研究仍然有限。

方法

本研究共纳入 342 名来自北京的原发性高血压患者。对每位患者进行改良的 Sullivan 急性口服盐水负荷和利尿收缩试验。通过问卷获得病史和生活方式危险因素。采用广义线性模型检验 29 个单核苷酸多态性(SNP)与 SSBP 的相关性,并采用错误发现率(FDR)校正多重检验的 P 值。

结果

在急性钠负荷过程中,校正年龄和 24 小时尿钠浓度后,CYP11B2、PRKG1、SLC8A1 基因的 SNP 与收缩压(SBP)在加性和隐性模型中呈显著正相关;CYP4A11、PRKG1、SLC8A1 和 ADRB2 基因的 SNP 与舒张压(DBP)呈显著正相关。在利尿收缩过程中,CLCNKA、eNOS、PRKG1 基因的 SNP 与 SBP 和 DBP 下降有关。经 FDR 校正后,SLC8A1 基因的 rs434082 仍与盐负荷时血压升高显著相关。在加性模型中,在调整年龄和 24 小时尿钠浓度后,A 等位基因使 DBP 增加 2.8mmHg(FDR_q=0.029),MAP 增加 3.1mmHg(FDR_q=0.029)。

结论

SLC8A1 基因可能在中国汉族人群急性钠负荷过程中导致血压变化。

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