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. CONCLUSION : 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.[1]References
- Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population. Balkestein, E.J., Wang, J.G., Struijker-Boudier, H.A., Barlassina, C., Bianchi, G., Birkenhäger, W.H., Brand, E., Den Hond, E., Fagard, R., Herrmann, S.M., Van Bortel, L.M., Staessen, J.A. J. Hypertens. (2002) [Pubmed]
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