The Association of Carotid Artery Intimal-Medial Thickness and Allelic Variants of Stromelysin-1, Interleukin-6 and Hepatic Lipase Genes: A Pilot Study from the Northern Manhattan Stroke Study
Objective: To determine the association between carotid artery intimal-medial thickness (IMT) and functional promoter variants of stromelysin-1 (MMP3: -16125A>6A), interleukin-6 (IL6: -174G>C) and hepatic lipase (HL: -480C>T) genes. Background: Carotid artery intimal-medial thickness (IMT) correlates well with pathologically defined atherosclerosis, a complex multifactorial disorder with both hereditary and environmental causes. IMT is also a risk factor for stroke, myocardial infarction and death. Methods: High-resolution B-mode imaging and mean intimal-medial thickness (IMT) measurements in common carotid arteries were obtained in 87 subjects (mean age 70±12 years; 55% women; race-ethnicity: 60% Hispanic, 35% black, 13% white) using a standardized carotid artery IMT protocol. Genotyping was assessed using PCR amplification and restriction digestion with enzymes specific to the alleles. Results: For all polymorphisms genotype distribution was as expected from Hardy-Weinberg proportions. The frequencies of the rare alleles at each locus in the sample were: MMP3 5A 0.32 (95% CI, 0.25–0.39), IL6 -174C 0.19 (95% CI, 0.13–0.25) and HL -480T 0.42 (95% CI, 0.35–0.50). For MMP3 and IL6, but not HL, these frequencies were significantly lower than reported in Caucasian subjects. The overall mean common carotid artery IMT was 0.86±0.20 mm. Subjects with the genotypes MMP3 6A6A or HL CC had 8% greater mean common carotid artery IMT than the other genotypes combined (MMP3 6A6A: 0.93 mm vs. 0.86 mm, absolute IMT difference =0.07 mm; HL CC: 0.93 mm vs. 0.86 mm, absolute IMT difference = 0.07 mm). Subjects with IL6 GG had 2% higher common carotid artery IMT compared to others combined (IL6 GG: 0.89 mm vs. 0.87 mm, absolute IMT difference). Conclusion: We observed higher common carotid artery intimal-medial thickness in subjects homozygous for specific candidate genes related to matrix deposition, lipid metabolism and inflammation. Further studies with increased power are needed to confirm these genotype-phenotipe associations.