Why the study?
Is there an association between carotid and femoral intima-media thickness and polymorphisms in the ACE, aldosterone synthase, and alpha-adducin genes in a Caucasian population?
Is there an association between carotid and femoral intima-media thickness and polymorphisms in the ACE, aldosterone synthase, and alpha-adducin genes in a Caucasian population?
Femoral intima-media thickness is associated with the ACE D allele, but this effect is dependent on the co-presence of alpha-adducin 460Trp or aldosterone synthase -344T alleles.
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Gene interactions may modulate femoral IMT; leaves open causal roles and clinical relevance of these polymorphisms in hypertension.
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.
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Balkestein et al. (2002) studied this question.
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