Carotid Intima-Media Thickness Is Associated With Allelic Variants of Stromelysin-1, Interleukin-6, and Hepatic Lipase Genes

Abstract

Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: -1612 5A>6A), interleukin-6 (IL6: -174G>C), and hepatic lipase (HL: -480C>T) genes. B-mode carotid ultrasound was performed among 87 subjects (mean age, 70+/-12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery). For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows: MMP3 -1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 -174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL -480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78+/-0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95+/-0.17 versus 0.87+/-0.15 mm; P=0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85+/-0.17 versus 0.76+/-0.16 mm; P=0.03), and those with the HL genotype CC had 13% greater IMT (0.87+/-20 versus 0.76+/-0.18 mm; P=0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations. Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 -16126A), inflammation (IL6 -174G), and lipid metabolism (HL -480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.