Aging, Carotid Artery Distensibility, and the Ser422Gly Elastin Gene Polymorphism in Humans

Abstract

Elastin is a protein of the extracellular matrix that forms the major component of elastic fibers from the arterial wall thickness and plays an important role in elastic properties of large blood vessels. To study the relationships between the Ser422Gly polymorphism in exon 16 of the gene-encoding elastin and the distensibility of 2 different arteries, the radial artery (a muscular artery) and the common carotid artery (an elastic artery), we studied a cohort of 320 subjects (49±12 years of age) without evidence of cardiovascular disease and who had never been treated with cardiovascular drugs. Distensibility and elastic modulus were evaluated for the common carotid and the radial arteries with high-resolution echo-tracking devices (NIUS-02 and Wall Track System). The A-to-G nucleotide change corresponding to the Ser422Gly amino acid change was studied by digestion of polymerase chain reaction products with Bst NI. Results indicate that genotype frequencies (AA=10%, AG=51%, GG=39%) were in agreement with the Hardy-Weinberg equilibrium. For the carotid artery, a significant decrease in distensibility was observed in subjects carrying the A allele (with AA+AG genotypes) compared with 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 allele. Moreover, the presence of the A allele was associated with a significant 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 genotypes, P <0.01). Multivariate analysis indicated that these results were observed 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 adjusted for mean arterial blood pressure indicated that the association between the A allele and distensibility of the carotid artery was observed only in subjects >50 years of age, assuming for carotid distensibility a significant age effect ( P <0.01), genotype effect ( P =0.01), and age-genotype interaction ( P =0.04). The present results indicate a relationship between the Ser422Gly 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.