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盐皮质激素受体多态性I180V与顽固性高血压左心室肥厚的关联

Association of Mineralocorticoid Receptor Polymorphism I180V With Left Ventricular Hypertrophy in Resistant Hypertension.

作者信息

Ritter Alessandra Mileni Versuti, Fontana Vanessa, Faria Ana Paula Cabral de, Modolo Rodrigo, Barbaro Natália R, Sabbatini Andréa R, Peres Heverton, Biagi Celso, Silva Pamela S, Lopes Paulo C, Tanus-Santos José Eduardo, Coelho Eduardo B, Moreno Heitor

机构信息

Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil;

Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, SP, Brazil;

出版信息

Am J Hypertens. 2016 Feb;29(2):245-50. doi: 10.1093/ajh/hpv070. Epub 2015 Jun 6.

Abstract

OBJECTIVES

Genetic polymorphisms on mineralocorticoid receptor gene (NC3C2) are associated with variability of mineralocorticoid receptor (MR) function and cardiovascular implications. We sought to investigate whether I180V (rs5522) and MRc.-2G_C (rs2070951) polymorphisms in NR3C2 gene are associated with resistance to antihypertensive treatment and target-organ damage in resistant hypertensive (RHTN) patients.

METHODS

One hundred and eighty-one RHTN and 122 mild to moderate hypertensive (HTN) patients were enrolled in this study. Genotypes were obtained by allelic discrimination assay using real-time polymerase chain reaction. We determined pulse wave velocity (PWV), microalbuminuria, and left ventricular mass index to assess target-organ damage. We compared clinical and laboratorial characteristics of AA vs. G carriers for rs5522 and AC vs. GG vs. CG for rs2070951.

RESULTS

We did not found differences in allele, genotype, and haplotype frequencies for both polymorphisms between HTN and RHTN subjects. We found increased levels of aldosterone and ambulatory blood pressure (BP) in G carriers only for rs5522. Left ventricular hypertrophy (LVH) was more prevalent in G carriers than AA homozygous for rs5522 but not for rs2070951 in RHTN. On the other hand, microalbuminuria and PWV were similar among genotypes for both polymorphisms. No differences were observed between the haplotypes, except for higher aldosterone concentration in GG compared to AG and AC haplotypes.

CONCLUSION

Our study suggests that rs5522 polymorphism might affect cardiac remodeling and aldosterone levels in RHTN subjects.

摘要

目的

盐皮质激素受体基因(NC3C2)的基因多态性与盐皮质激素受体(MR)功能的变异性及心血管影响相关。我们旨在研究NR3C2基因中的I180V(rs5522)和MRc.-2G_C(rs2070951)多态性是否与顽固性高血压(RHTN)患者的降压治疗抵抗及靶器官损害相关。

方法

本研究纳入了181例RHTN患者和122例轻至中度高血压(HTN)患者。通过实时聚合酶链反应的等位基因鉴别分析获得基因型。我们测定了脉搏波速度(PWV)、微量白蛋白尿和左心室质量指数以评估靶器官损害。我们比较了rs5522的AA与G携带者以及rs2070951的AC与GG与CG的临床和实验室特征。

结果

我们未发现HTN和RHTN受试者之间这两种多态性的等位基因、基因型和单倍型频率存在差异。仅对于rs5522,我们发现G携带者的醛固酮水平和动态血压(BP)升高。在RHTN中,rs5522的G携带者比AA纯合子更易发生左心室肥厚(LVH),但rs2070951并非如此。另一方面,两种多态性的基因型之间微量白蛋白尿和PWV相似。除了GG单倍型的醛固酮浓度高于AG和AC单倍型外,单倍型之间未观察到差异。

结论

我们的研究表明,rs5522多态性可能影响RHTN受试者的心脏重塑和醛固酮水平。

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