January 2001, Volume 15, Issue 1, Pages 49 – 55

Original Article

Haplotypes of the human renin gene associated with essential hypertension and stroke PM Frossard1, MJ Malloy2, GG Lestringant3 & JP Kane2 1Department of Pathology, Faculty of Medicine and Health Sciences, Al Ain, United Arab Emirates     2Cardiovascular Research Center, University of California San Francisco, San Francisco, CA, USA     3Department of Internal Medicine, Tawam Hospital, Al Ain, UAE     Correspondence to: Philippe M Frossard, Department of Pathology, Faculty of Medicine & Health Sciences, PO Box 17666, Al Ain, United Arab Emirates. E-mail: frossard@emirates.net.ae

Keywords

case-control studies;   genetics;   hypertension, essential;   polymerase chain reaction;   renin

Abstract

The human renin gene (REN) is a good candidate in studies aimed at unravelling the genetic basis of essential hypertension and stroke. We previously established that both a BglI and an MboI dimorphisms (located respectively in the first and ninth introns of the REN gene) were associated with essential hypertension in a population of hyperlipidaemic US subjects. In this association (retrospective case-control) study, we investigated the haplotype distribution of alleles defined by the combination of REN BglI and MboI dimorphic sites in 329 hyperlipidaemic US Caucasian subjects referred to UCSF Medical Center (140 hypertensives, 141 normotensives, and 48 hypertensive patients who had suffered a stroke). A statistically significant association was found between alleles determined by both (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) haplotypes and clinical diagnosis of EHT (combined odds ratios, OR = 3.35, corrected P < 10-7). Haplotypes (-,+) and (+,+) were also found to be associated with clinical diagnosis of stroke (OR = 4.31, P < 10-7). These associations do not occur through the effects of classical risk factors related to lipid, lipoprotein and apolipoprotein levels. We conclude that variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with REN (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) alleles could play a role in contributing to increased individual’s genetic susceptibility to EHT and to stroke. Journal of Human Hypertension(2001) 15, 49-55

Received 19 April 2000; Revised 5 June 2000; Accepted 6 June 2000

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