Epistatic interactions between the ACE, ADD and AS genes contribute to the prevalence and incidence of hypertension in Caucasians. The clinical relevance of the risk-conferring haplotypes identified in our prospective study was underscored by their positive predictive values, which under the assumption of a 20% life-time risk of hypertension, ranged from 29.8-40.1%.

Abstract-Different genetic polymorphisms influence cardiovascular disease. We recently discovered a relationship between the intima-media thickness of the muscular femoral artery, but not the elastic common carotid artery, and the combined ACE (ACE, I/D), ␣-adducin (Gly460Trp), and aldosterone synthase (AS, CϪ344T) gene polymorphisms. To investigate the relationship between these polymorphisms and functional properties of the carotid artery and femoral artery, a sample of 756 subjects enrolled in a population study were genotyped for the presence of the ACE D, ␣-adducin 460Trp, and aldosterone synthase Ϫ344T alleles. Vessel wall properties were assessed using a vessel wall movement detector system in combination with applanation tonometry. Statistical analysis allowed for confounders and interaction among genes. Cross-sectional compliance of the common carotid artery was negatively associated with the ACE D allele. ACE II versus ACE DD homozygotes differed, expressed as a percentage of the population mean (7.0%; 95% confidence interval [CI], 1.6% to 12.4%; Pϭ0.02). In multigene analysis, ACE DD subjects also deviated significantly from the population mean for the distensibility coefficient of the common carotid artery when carrying the AS/T allele (Ϫ5.5%; 95% CI, Ϫ9.3% to Ϫ1.7%; PϽ0.01), without a change in cross-sectional compliance. ACE DD subjects, when homozygote for ␣-adducin Gly460, had a lower femoral cross-sectional compliance (Ϫ10.4%; 95% CI, Ϫ1.9% to Ϫ18.9%; PϽ0.03) and a lower distensibility (Ϫ9.7%; 95% CI, Ϫ2.1% to Ϫ17.3%; PϽ0.02) compared with the population mean. These data show that functional large artery properties are influenced by the ACE I/D polymorphism. Cross-sectional compliance and distensibility coefficients are influenced by the ACE I/D genotype, but this influence depends on the vascular territory and genetic background.

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