CYP11B2 基因单倍型独立且与醛固酮和醛固酮与肾素比值共同增加高血压风险。

CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension.

机构信息

Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.

出版信息

Clin Biochem. 2010 Jan;43(1-2):136-41. doi: 10.1016/j.clinbiochem.2009.09.015. Epub 2009 Sep 26.

DOI:10.1016/j.clinbiochem.2009.09.015

PMID:19786005

Abstract

OBJECTIVES

Aldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure. Polymorphisms in aldosterone-synthase gene (CYP11B2) may associate with heterogeneous aldosterone production and hypertension. Hence, we investigated -344T/C, Iw/Ic polymorphisms of CYP11B2, plasma renin activity (PRA) and aldosterone concentration (PAC).

DESIGN AND METHODS

Consecutive ethnically-matched 450 hypertensive patients and 360 controls were screened by PCR-RFLP for genotypes and haplotypes; PRA and PAC were measured.

RESULTS

The Iw/Ic polymorphism distribution differed significantly between the two groups (LRT chi(2)=15.8, df=2, P=0.000). The mutant allele-Ic and genotype-Ic/Ic were overrepresented in patients (35% versus 27% and 13% versus 7%). Overrepresentation of T-Ic haplotype in patients was identified as risk haplotype (P=0.000). Patients had significantly higher PAC and aldosterone-to-renin ratio (ARR; P=0.000), which was Ic-allele dependent.

CONCLUSIONS

The haplotype T-Ic associated with hypertension susceptibility. Correlation between Ic-allele and raised ARR likely serve in hypertension management.

摘要

目的

醛固酮合酶产生醛固酮，调节电解质，从而调节血压。醛固酮合酶基因（CYP11B2）的多态性可能与醛固酮生成和高血压的异质性有关。因此，我们研究了 CYP11B2 的-344T/C、Iw/Ic 多态性、血浆肾素活性（PRA）和醛固酮浓度（PAC）。

设计和方法

通过 PCR-RFLP 对连续的、种族匹配的 450 名高血压患者和 360 名对照者进行基因型和单倍型筛查；测量 PRA 和 PAC。

结果

Iw/Ic 多态性在两组间的分布差异有统计学意义（LRT chi(2)=15.8, df=2, P=0.000）。突变等位基因-Ic 和基因型-Ic/Ic 在患者中更为常见（35%比 27%和 13%比 7%）。在患者中，T-Ic 单倍型的过度表达被确定为风险单倍型（P=0.000）。患者的 PAC 和醛固酮与肾素比值（ARR；P=0.000）显著升高，这与 Ic 等位基因有关。