title: Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population.
abstract: BACKGROUND
  In a Caucasian population, the prevalence and incidence of hypertension, renal function and large artery stiffness were significantly correlated with polymorphisms in the genes encoding the angiotensin-converting enzyme (ACE I/D), aldosterone synthase (-C344T) and the cytoskeleton protein alpha-adducin (Gly460Trp).
  
  
  OBJECTIVE
  This study investigated intima-media thickening, a precursor of atherosclerosis, in relation to these genetic polymorphisms.
  
  
  METHODS
  Carotid and femoral intima-media thickness were assessed with a wall-track system in 380 subjects enrolled in a population study. Subjects were genotyped for the presence of the ACE D, aldosterone synthase -344T and alpha-adducin 460Trp alleles. The statistical analysis allowed for confounders, interactions among genes, and the non-independence of the phenotypes within families.
  
  
  RESULTS
  The sample included 188 men (49.5%). Mean age was 39.8 years. Intima-media thickness of the carotid and femoral arteries averaged 575 and 719 microm, respectively. Intima-media thickness of the femoral-but not carotid-artery increased with the number of ACE D alleles. The effect of ACE genotype on femoral intima-media thickness was confined to carriers of the 460Trp allele and the -344T allele. Expressed as a percentage of the population mean, the mean differences between II and DD homozygotes averaged 13.4% (95% CI 5.6-21.2%) in all subjects, 21.2% (8.0-34.5%) in carriers of the 460Trp allele, 15.4% (4.1-26.8%) in carriers of the -344T allele, and 25.2% (10.7-39.7%) if the 460Trp and -344T alleles were both present.
  
  
  CONCLUSIONS
  This study shows that a relationship exists between the intima-media thickness of the large muscular femoral artery and the ACE gene. This relationship is only apparent in the presence of either the alpha-adducin 460Trp or the aldosterone synthase -344T allele. These findings may have clinical implications for the assessment of genetic cardiovascular risk.
authors.affiliation: Cardiovascular Research Institute Maastricht, Capaciteitsgroep Farmakologie en Toxicologie, Universiteit Maastricht, Maastricht, The Netherlands.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Balkestein
authors.forename: Ji Guang
authors.initials: JG
authors.lastname: Wang
authors.forename: Harry A J
authors.initials: HA
authors.lastname: Struijker-Boudier
authors.forename: Cristina
authors.initials: C
authors.lastname: Barlassina
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
authors.forename: Willem H
authors.initials: WH
authors.lastname: Birkenhäger
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
authors.forename: Elly
authors.initials: E
authors.lastname: Den Hond
authors.forename: Robert
authors.initials: R
authors.lastname: Fagard
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Herrmann
authors.forename: Luc M
authors.initials: LM
authors.lastname: Van Bortel
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001161:Arteriosclerosis / Q000235:genetics; D001483:Base Sequence; D001530:Belgium; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000235:genetics*; D002648:Child; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014463:Ultrasonography; D044465:White People / Q000235:genetics*; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D019405:Cytochrome P-450 CYP11B2; D004247:DNA; D007703:Peptidyl-Dipeptidase A; D000099291:Adducins