Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population.
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.
Balkestein
Elisabeth J
EJ
Cardiovascular Research Institute Maastricht, Capaciteitsgroep Farmakologie en Toxicologie, Universiteit Maastricht, Maastricht, The Netherlands.
Wang
Ji Guang
JG
Struijker-Boudier
Harry A J
HA
Barlassina
Cristina
C
Bianchi
Giuseppe
G
Birkenhäger
Willem H
WH
Brand
Eva
E
Den Hond
Elly
E
Fagard
Robert
R
Herrmann
Stefan-Martin
SM
Van Bortel
Luc M
LM
Staessen
Jan A
JA
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
D002148:Calmodulin-Binding Proteins; D019405:Cytochrome P-450 CYP11B2; D004247:DNA; D007703:Peptidyl-Dipeptidase A; D000099291:Adducins