Yasuda H, Kamide K, Takiuchi S, Matayoshi T, Hanada H, Kada A, Yang J, Miwa Y, Yoshii M, Horio T, Yoshihara F, Nakamura S, Nakahama H, Tei C, Miyata T, Kawano Y
Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka, Japan.
J Hum Hypertens. 2007 Nov;21(11):883-92. doi: 10.1038/sj.jhh.1002234. Epub 2007 May 24.
Endothelin-1 (ET-1) is a potent vasoconstrictive peptide and its activity is mediated by the receptors ET type A (EDNRA) and ET type B (EDNRB). Although ET-1 is thought to play an important role in the development of atherosclerosis, it remains unclear whether polymorphisms of ET-1 family genes, including the ET-1 gene (EDN1), EDNRA, EDNRB and the genes for endothelin converting enzymes 1 and 2 (ECE1 and ECE2), are associated with the progression of atherosclerosis. We investigated the relationship between 11 single nucleotide polymorphisms (SNPs) of ET-1 family genes (including three in EDN1, one in EDNRA, two in EDNRB, four in ECE1 and one in ECE2) and atherosclerotic changes assessed using pulse wave velocity (PWV) and carotid ultrasonography in 630 patients with essential hypertension (EHT). In male subjects, we found significant differences in brachial-ankle PWV (baPWV) in additive and recessive models in EDNRB-rs5351 after Bonferroni correction. Also in male subjects, there were significant differences in mean intima-media thickness (IMT) in additive and recessive models in EDNRA-rs5333 after Bonferroni correction. We found no significant correlation between any SNPs in the ET family genes and baPWV, IMT and Plaque score (PS) in female subjects. Furthermore, after multiple logistic regression analysis, only EDNRB-rs5351 indicated as an independent risk of atherosclerosis in male hypertensive subjects. Of the endothelin-related genes, EDNRB-rs5351 was the most susceptible SNP associated with atherosclerosis in male hypertensives, and the genetic background may be involved in the progression of atherosclerosis in EHT patients.
内皮素 -1（ET-1）是一种强效血管收缩肽，其活性由A型内皮素受体（EDNRA）和B型内皮素受体（EDNRB）介导。尽管ET-1被认为在动脉粥样硬化的发展中起重要作用，但ET-1家族基因的多态性，包括ET-1基因（EDN1）、EDNRA、EDNRB以及内皮素转化酶1和2（ECE1和ECE2）的基因，是否与动脉粥样硬化的进展相关仍不清楚。我们调查了630例原发性高血压（EHT）患者中ET-1家族基因的11个单核苷酸多态性（SNP）（包括EDN1中的3个、EDNRA中的1个、EDNRB中的2个、ECE1中的4个和ECE2中的1个）与使用脉搏波速度（PWV）和颈动脉超声评估的动脉粥样硬化变化之间的关系。在男性受试者中，经Bonferroni校正后，EDNRB-rs5351在加性和隐性模型中的臂踝PWV（baPWV）存在显著差异。同样在男性受试者中，经Bonferroni校正后，EDNRA-rs5333在加性和隐性模型中的平均内膜中层厚度（IMT）存在显著差异。我们发现女性受试者中ET家族基因的任何SNP与baPWV、IMT和斑块评分（PS）之间均无显著相关性。此外，经过多因素逻辑回归分析，仅EDNRB-rs5351被表明是男性高血压受试者动脉粥样硬化的独立危险因素。在内皮素相关基因中，EDNRB-rs5351是男性高血压患者中与动脉粥样硬化最相关的易感SNP，其遗传背景可能参与了EHT患者动脉粥样硬化的进展。
