Carotid Intima-Media Thickness Is Associated With Allelic Variants of Stromelysin-1, Interleukin-6, and Hepatic Lipase Genes: The Northern Manhattan Prospective Cohort Study

Abstract

Background and Purpose — 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. Methods — 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). Results — 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. Conclusions — 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.