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肾素-血管紧张素-醛固酮系统基因变异对新诊断高血压患者高血压严重程度的影响。

Impact of renin-angiotensin-aldosterone system gene variants on the severity of hypertension in patients with newly diagnosed hypertension.

作者信息

Tiago Armindo D, Badenhorst Danelle, Nkeh Benedicta, Candy Geoffrey P, Brooksbank Richard, Sareli Pinhas, Libhaber Elena, Samani Nilesh J, Woodiwiss Angela J, Norton Gavin R

机构信息

Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand, Parktown, Johannesburg, South Africa.

出版信息

Am J Hypertens. 2003 Dec;16(12):1006-10. doi: 10.1016/j.amjhyper.2003.07.010.

Abstract

BACKGROUND

The severity of hypertension has prognostic significance. Previous studies have assessed the relationship between renin-angiotensin-aldosterone system (RAAS) genotype and the severity of hypertension in either treated patients or those who have only recently discontinued treatment.

METHODS

We assessed the impact of RAAS genotype on ambulatory and office blood pressure (BP) in 231 newly diagnosed hypertensive patients of African ancestry who had never received therapy. Subjects were genotyped for variants of the angiotensin-converting enzyme (insertion/deletion), angiotensinogen (M235T, -20A-->C), and aldosterone synthase (CYP11B2)(-344C-->T) genes.

RESULTS

The CYP11B2 gene polymorphism was associated with systolic BP (SBP). In comparison to subjects with at least one copy of the -344C allele (n = 75), patients who were homozygous for the -344T allele (n = 156) had both higher ambulatory SBP (150 +/- 1 v 144 +/- 1 mm Hg, P =.002 before and P =.01 after adjusting for multiple genotyping) and office SBP (163 +/- 2 v 156 +/- 2 mm Hg, P =.01 before and P =.05 after adjusting for multiple genotyping). Neither the angiotensin-converting enzyme insertion/deletion nor the angiotensinogen gene polymorphisms were associated with ambulatory or office SBP or diastolic BP (DBP). The CYP11B2 gene variant also did not affect DBP.

CONCLUSION

A variant within the CYP11B2 locus has a clinically important impact on the severity of SBP changes in individuals with newly diagnosed hypertension who are of African ethnicity.

摘要

背景

高血压的严重程度具有预后意义。既往研究评估了肾素-血管紧张素-醛固酮系统(RAAS)基因型与已接受治疗患者或刚停药患者的高血压严重程度之间的关系。

方法

我们评估了RAAS基因型对231例从未接受过治疗的非洲裔新诊断高血压患者动态血压和诊室血压(BP)的影响。对受试者进行血管紧张素转换酶(插入/缺失)、血管紧张素原(M235T、-20A→C)和醛固酮合酶(CYP11B2)(-344C→T)基因变异的基因分型。

结果

CYP11B2基因多态性与收缩压(SBP)相关。与至少有一个-344C等位基因拷贝的受试者(n =  75)相比,-344T等位基因纯合子患者(n = 156)的动态SBP(150±1对144±1 mmHg,多重基因分型校正前P = .002,校正后P = .01)和诊室SBP(163±2对156±2 mmHg,多重基因分型校正前P = .01,校正后P = .05)均较高。血管紧张素转换酶插入/缺失和血管紧张素原基因多态性均与动态或诊室SBP或舒张压(DBP)无关。CYP11B2基因变异也不影响DBP。

结论

CYP11B2基因座内的一个变异对新诊断的非洲裔高血压个体SBP变化的严重程度具有重要临床影响。

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