title: 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.
authors.affiliation: Cardiovascular Research Institute Maastricht, Department of Pharmacology, Maastricht University, Maastricht, The Netherlands. e.balkestein@farmaco.unimaas.nl
authors.forename: E J
authors.initials: EJ
authors.lastname: Balkestein
authors.forename: J A
authors.initials: JA
authors.lastname: Staessen
authors.forename: J G
authors.initials: JG
authors.lastname: Wang
authors.forename: J J
authors.initials: JJ
authors.lastname: van Der Heijden-Spek
authors.forename: L M
authors.initials: LM
authors.lastname: Van Bortel
authors.forename: C
authors.initials: C
authors.lastname: Barlassina
authors.forename: G
authors.initials: G
authors.lastname: Bianchi
authors.forename: E
authors.initials: E
authors.lastname: Brand
authors.forename: S M
authors.initials: SM
authors.lastname: Herrmann
authors.forename: H A
authors.initials: HA
authors.lastname: Struijker-Boudier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019412:Anatomy, Cross-Sectional; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics / Q000503:physiopathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000502:physiology*; D002648:Child; D003187:Compliance; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D014463:Ultrasonography; D044465:White People / Q000235:genetics*; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A; D000099291:Adducins