Carotid and femoral artery stiffness in relation to three candidate genes in a white population

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), alpha-adducin (Gly460Trp),and aldosterone synthase (AS, C-344T) 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, alpha-adducin 460Trp, and aldosterone synthase -344T 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%; P=0.02). 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 (-5.5%; 95% CI, -9.3% to -1.7%; P<0.01), without a change in cross-sectional compliance. ACE DD subjects, when homozygote for alpha-adducin Gly460, had a lower femoral cross-sectional compliance (-10.4%; 95% CI, -1.9% to -18.9%; P<0.03) and a lower distensibility (-9.7%; 95% CI, -2.1% to -17.3%; P<0.02) 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.