Association of human renin gene haplotype with essential hypertension in an isolated population

Abstract

Among the many candidates that could be implicated in underlying an individual's genetic susceptibility to human essential hypertension (EHT), the renin gene (REN) is particularly appealing because of its central role in the renin-angiotensin-aldosterone system and of its demonstrated functional role in hypertensive animal models.We had previously shown that two dimorphic sites of the human REN gene (BglI in intron 1 and MboI in intron 9) were individually associated with hypertension in two independent populations.We used here a retrospective, case-control design to investigate the haplotype distributions of alleles combining BglI and MboI sites in two groups of subjects (144 hypertensives and 96 normotensives) from the United Arab Emirates (UAE), a genetically homogeneous ethnic population with no history of smoking or alcohol consumption. There was a marked difference in the distribution of haplotypes among normotensive vs. hypertensive subjects (χ2 = 29.87, 3 df, p=10−6). The odds ratio of the association of [BglI(+)-MboI(+)] haplotypes with increased risk for hypertension was 4.43 (95% CI: 2.41–8.19, Yates-corrected p = 3 × 10−7).Genetic variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with REN [BglI(+)-MboI(+)] alleles could play a role in contributing to increased individual's genetic susceptibility to EHT among UAE nationals studied here.