A型内皮素受体单倍型与冠心病死亡率之间的关联。

Association between endothelin type A receptor haplotypes and mortality in coronary heart disease.

作者信息

Ellis Katrina L, Pilbrow Anna P, Potter Howard C, Frampton Chris M, Doughty Rob N, Whalley Gillian A, Ellis Chris J, Palmer Barry R, Skelton Lorraine, Yandle Tim G, Troughton Richard W, Richards A Mark, A Cameron Vicky

机构信息

Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand.

Molecular Pathology Laboratory, Canterbury District Health Board, Christchurch, New Zealand.

出版信息

Per Med. 2012 May;9(3):341-349. doi: 10.2217/pme.12.10.

DOI:10.2217/pme.12.10

PMID:29758796

Abstract

AIMS

The endothelin type A receptor, encoded by EDNRA, mediates the effects of endothelin-1 to promote vasoconstriction, vascular cell growth, adhesion, fibrosis and thrombosis. We investigated the association between EDNRA haplotype and cardiovascular outcomes in patients with coronary artery disease.

METHODS

Coronary disease patients (n = 1007) were genotyped for the His323His (rs5333) variant and one tag SNP from each of the major EDNRA haplotype blocks (rs6537484, rs1568136, rs5335 and rs10003447). EDNRA haplotype associations with clinical history, natriuretic peptides cardiac function and cardiovascular outcomes were tested over a median 3.8 years.

RESULTS

Univariate analysis identified a 'low-risk' EDNRA haplotype associated with later age of Type 2 diabetes onset (p = 0.004) smaller BMI (p = 0.021), and reduced mortality (log rank p = 0.001). Cox proportional hazards analysis including established cardiovascular risk factors revealed an independent association between haplotype and mortality (p < 0.0001).

CONCLUSION

These data highlight the potential importance of the endothelin system, and in particular EDNRA in coronary disease.

摘要

目的

由EDNRA编码的内皮素A型受体介导内皮素-1的作用，以促进血管收缩、血管细胞生长、黏附、纤维化和血栓形成。我们研究了EDNRA单倍型与冠心病患者心血管结局之间的关联。

方法

对1007例冠心病患者进行His323His（rs5333）变异以及来自每个主要EDNRA单倍型块的一个标签单核苷酸多态性（rs6537484、rs1568136、rs5335和rs10003447）的基因分型。在中位3.8年的时间里，测试EDNRA单倍型与临床病史、利钠肽心功能和心血管结局之间的关联。