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Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes - The Northern Manhattan Prospective Cohort Study.
1420 - 1423.
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.
|Title:||Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes - The Northern Manhattan Prospective Cohort Study|
|Location:||FT LAUDERDALE, FL|
|Keywords:||genetics, interleukin-6, intima-media thickness, lipase, stromelysin 1, ultrasonography, PROMOTER POLYMORPHISMS, ARTERIAL-WALL, ATHEROSCLEROSIS, DETERMINANTS, DISEASE, STROKE, ADULTS, RISK|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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