393 ORIGINAL ARTICLE Neuroendocrinology Letters No.4 August Vol.26, 2005 Copyright © 2005 Neuroendocrinology Letters ISSN 0172–780X www.nel.edu Association of ace polymorphisms with left ventricular hypertrophy Mohammad Saeed 1 , Sammer Siddiqui 1 , Aisha Khan 1 , Zahid A. Butt 1 , S. Hasan Parvez 2 & Philippe M. Frossard 1 1 Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan; 2 Neuroendocrinology and Neuropharmacology Unit, CNRS, Gif-sur-Yvette, France. Correspondence to: Dr. Philippe M. Frossard Department of Biological and Biomedical Sciences he Aga Khan University Stadium Road, P. O. Box 3500, Karachi – 74800, PAKISTAN TEL : +92 (21) 4859 4540 FAX : +92 (21) 493 4294 EMAIL : philippe.frossard@aku.edu Submitted: September 23, 2004 Accepted: October 15, 2004 Key words: ace gene; polymorphisms; haplotypes; association; let ventricular hypertrophy Neuroendocrinol Lett 2005; 26(4):393–396 PMID: 16136003 NEL260405A17 © Neuroendocrinology Letters www.nel.edu Abstract he angiotensin converting enzyme gene (ACE) is a candidate gene for an indi- vidual’s genetic susceptibility to let 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 inluenced by a unique set of hormonal, vascular and genetic factors. In this study, we attempted to determine whether two representative poly- morphisms of the ACE gene, ACE I/D and 2350 G>A, known to be associated with EH and to inluence plasma ACE levels most signiicantly, 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 – an ethnic group characterized by no alcohol intake and no cigarette smoking – for correlations with LVH. Clinical diagnosis of LVH was based on echocardiographic and ECG criteria. ACE I/D and 2350 G>A genotypes were determined by PCR and restric- tion digestion. Univariate and multivariate logistic regression analyses revealed an association between ACE polymorphisms and LVH. Haplotype analysis further supported this inding. ACE I/D and ACE 2350 G>A polymorphisms are in strong linkage disequilibrium and are associated with LVH, suggesting that ACE is likely to be a QTL for LVH. Introduction Left ventricular hypertrophy (LVH), a major independent cardiovascular risk factor for mortal- ity, is widely believed to be a consequence of essen- tial hypertension (EH) [Cambien et al ., 1992]. There is now some evidence that LVH is an inde- pendent clinical entity, with its own unique genetic and environmental influences, rather than solely an end point of EH [Ganau et al., 1990; Drayer et al., 1983]. Neuroendocrine factors such as angiotensin II have also been implicated in the etiopathogen-