Aging, carotid artery distensibility, and the Ser422Gly elastin gene polymorphism in humans

Elastin is a protein of the extracellular matrix that forms the major compo nent of elastic fibers from the arterial wall thickness and plays an import ant role in elastic properties of large blood vessels. To study the relatio nships between the Ser422Gly polymorphism in exon 16 of the gene-encoding e lastin and the distensibility of 2 different arteries, the radial artery (a muscular artery) and the common carotid artery (an elastic artery), we stu died a cohort of 320 subjects (49 +/- 12 years of age) without evidence of cardiovascular disease and who had never been treated with cardiovascular d rugs. Distensibility and elastic modulus were evaluated for the common caro tid and the radial arteries with high-resolution echo-tracking devices (NIU S-02 and Wall Track System). The A-to-G nucleotide change corresponding to the Ser422Gly amino acid change was studied by digestion of polymerase chai n reaction products with BstNI. Results indicate that genotype frequencies (AA=10%, AG=51%, GG=39%) were in agreement with the Hardy-Weinberg equilibr ium. For the carotid artery, a significant decrease in distensibility was o bserved in subjects carrying the A allele (with AA+AG genotypes) compared w ith subjects with the GG genotype (13.8 +/-6.4 kPa(-1 .) 10(-3) versus 15.9 +/-6.2 kPa(-1 .) 10(-3), p <0.01), assuming a dominant effect of the A all ele. Moreover, the presence of the A allele was associated with a significa nt increase in elastic modulus (0.98 +/-0.40 kPa (.) 10(3) in subjects with AA+AG genotypes versus 0.83 +/-0.41 kPa (.) 10(3) in subjects with GG geno types, P <0.01). Multivariate analysis indicated that these results were ob served after adjustment for age, gender, and mean arterial blood pressure ( P <0.01). In contrast. no association was found between arterial parameters and genotypes for the radial artery. The 2-way analysis of covariance adju sted for mean arterial blood pressure indicated that the association betwee n the A allele and distensibility of the carotid artery was observed only i n subjects > 50 years of age, assuming for carotid distensibility a signifi cant age effect (P <0.01), genotype effect (P=0.01), and age-genotype inter action (P=0.04). The present results indicate a relationship between the Se r422Gly polymorphism and the distensibility of elastic arteries but not of muscular arteries and suggest that there is an age-genotype interaction for carotid artery distensibility.