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

Different genetic polymorphisms influence cardiovascular disease. We recent ly discovered a relationship between the intima-media thickness of the musc ular femoral artery, but not the elastic common carotid artery, and the com bined ACE (ACE, I/D), alpha -adducin (Gly460Trp), and aldosterone synthase (AS, C-344T) gene polymorphisms. To investigate the relationship between th ese polymorphisms and functional properties of the carotid artery and femor al artery, a sample of 756 subjects enrolled in a population study were gen otyped for the presence of the ACE D, alpha -adducin 460Trp, and aldosteron e synthase -344T alleles. Vessel wall properties were assessed using a vess el 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 asso ciated with the ACE D allele. ACE II versus ACE DD homozygotes differed, ex pressed as a percentage of the population mean (7.0%; 95% confidence interv al [CI], 1.6% to 12.4%; P=0.02). In multigene analysis, ACE DD subjects als o deviated significantly from the population mean for the distensibility co efficient 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 c ompliance. ACE DD subjects, when homozygote for a-adducin Gly460, had a low er 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 IID polymorphism. Cross-section al compliance and distensibility coefficients are influenced by the ACE IID genotype, but this influence depends on the vascular territory and genetic background.