Saeed Mohammad, Saleheen Danish, Siddiqui Sammer, Khan Aisha, Butt Zahid A, Frossard Philippe M
From the Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Hypertens Res. 2005 Apr;28(4):345-9. doi: 10.1291/hypres.28.345.
The angiotensin converting enzyme gene (ACE) is of much interest as a candidate gene conferring an individual's genetic susceptibility to left ventricular hypertrophy (LVH). LVH has long been thought to be an end point of essential hypertension (EH), rather than a separate entity, though it is influenced by a unique set of hormonal, vascular and genetic factors. In this study, we attempted to determine whether two representative polymorphisms of the ACE gene, ACE I/D and 2350 G>A, known to be associated with EH and to have a highly significant influence on plasma ACE levels, could implicate ACE as a quantitative trait locus (QTL) for LVH. We carried out a retrospective, case-control study of the two ACE polymorphisms amongst 180 nationals (50 LVH patients and 130 controls) from the United Arab Emirates (Emirati)--an ethnic group characterized by an absence of alcohol intake and cigarette smoking--for putative correlations with LVH. Clinical diagnoses of LVH were based on echocardiographic and ECG criteria. ACE I/D and 2350 G>A genotypes were determined by polymerase chain reaction (PCR) and restriction digestion. Univariate and multivariate logistic regression analyses revealed an association between ACE polymorphisms and LVH. Haplotype analysis further supported this finding. The ACE I/D and ACE 2350 G>A polymorphisms were in strong linkage disequilibrium and were independently associated with LVH, suggesting that ACE is likely to be a QTL for LVH. In conclusion, This is the first association study of the ACE 2350 G>A polymorphism with LVH; the results showed that this polymorphism, along with ACE I/D, is associated with LVH.
血管紧张素转换酶基因（ACE）作为赋予个体左心室肥厚（LVH）遗传易感性的候选基因备受关注。长期以来，LVH一直被认为是原发性高血压（EH）的终点，而非一个独立的实体，尽管它受到一组独特的激素、血管和遗传因素的影响。在本研究中，我们试图确定ACE基因的两个代表性多态性，即已知与EH相关且对血浆ACE水平有高度显著影响的ACE I/D和2350 G>A，是否能表明ACE是LVH的数量性状基因座（QTL）。我们对来自阿拉伯联合酋长国（阿联酋人）的180名国民（50名LVH患者和130名对照）进行了一项回顾性病例对照研究，该族群的特点是不饮酒和不吸烟，以寻找与LVH的假定相关性。LVH的临床诊断基于超声心动图和心电图标准。通过聚合酶链反应（PCR）和限制性酶切确定ACE I/D和2350 G>A基因型。单变量和多变量逻辑回归分析显示ACE多态性与LVH之间存在关联。单倍型分析进一步支持了这一发现。ACE I/D和ACE 2350 G>A多态性处于强连锁不平衡状态，且与LVH独立相关，这表明ACE可能是LVH的QTL。总之，这是首次关于ACE 2350 G>A多态性与LVH的关联研究；结果表明，该多态性与ACE I/D一起，与LVH相关。
