Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Dis Markers. 2012;32(1):33-41. doi: 10.3233/DMA-2012-0858.
Left ventricular dysfunction (LVD), followed by fall in cardiac output is one of the major complications in some coronary artery disease (CAD) patients. The decreased cardiac output over time leads to activation of the renin-angiotensin-aldosterone system which results in vasoconstriction by influencing salt-water homeostasis. Therefore, the purpose of the present study was to explore the association of single nucleotide polymorphisms (SNPs) in angiotensin I converting enzyme; ACE (rs4340), angiotensin II type1 receptor; AT1 (rs5186) and aldosterone synthase; CYP11B2 (rs1799998) with LVD.
The present study was carried out in two cohorts. The primary cohort included 308 consecutive patients with angiographically confirmed CAD and 234 healthy controls. Among CAD, 94 with compromised left ventricle ejection fraction (LVEF ⩽ 45) were categorized as LVD. The ACE I/D, AT1 A1166C and CYP11B2 T-344C polymorphisms were determined by PCR. Our results showed that ACE I/D was significantly associated with CAD but not with LVD. However, AT1 1166C variant was significantly associated with LVD (LVEF ⩽ 45) (p value=0.013; OR=3.69), but CYP11B2 (rs1799998) was not associated with either CAD or LVD. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.020; OR=5.20).
AT1 A1166C plays important role in conferring susceptibility of LVD.
左心室功能障碍（LVD），随后心输出量下降是某些冠状动脉疾病（CAD）患者的主要并发症之一。随着时间的推移，心输出量的减少会导致肾素-血管紧张素-醛固酮系统的激活，从而通过影响盐-水稳态导致血管收缩。因此，本研究旨在探讨血管紧张素 I 转换酶（ACE）中的单核苷酸多态性（SNP）；ACE（rs4340）、血管紧张素 II 型 1 受体；AT1（rs5186）和醛固酮合酶；CYP11B2（rs1799998）与 LVD 的关系。
本研究分为两个队列进行。主要队列包括 308 例经血管造影证实的 CAD 连续患者和 234 例健康对照者。在 CAD 中，94 例左心室射血分数（LVEF ⩽ 45）受损的患者被归类为 LVD。通过 PCR 确定 ACE I/D、AT1 A1166C 和 CYP11B2 T-344C 多态性。我们的结果表明，ACE I/D 与 CAD 显著相关，但与 LVD 无关。然而，AT1 1166C 变体与 LVD（LVEF ⩽ 45）显著相关（p 值=0.013；OR=3.69），但 CYP11B2（rs1799998）与 CAD 或 LVD 均无关。为了验证我们的结果，我们在另外 200 例具有相似临床特征的病例中进行了复制研究，结果再次证实了一致的发现（p 值=0.020；OR=5.20）。
AT1 A1166C 在赋予 LVD 易感性方面发挥重要作用。
