The MCP-1-2578G allele was significantly associated with a higher prevalence of myocardial infarction (adjusted OR 2.0; 95% CI 1.2-3.3; P=0.005) and higher serum MCP-1 levels.
Cohort (n=3,236)
Is the MCP-1-2578G allele associated with higher serum MCP-1 levels and prevalent myocardial infarction in a community-based cohort?
Genetic variation in the CCL2 gene (MCP-1-2578G allele) is associated with higher serum MCP-1 levels and an increased prevalence of myocardial infarction, supporting its role in human atherosclerosis.
Odds Ratio: 2 (95% CI 1.2–3.3)
p-value: p=0.005
BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine strongly implicated in promoting atherosclerosis in animal models, but human genetic evidence is contradictory. METHODS AND RESULTS: We analyzed the association of genetic variation in the MCP-1 gene (CCL2) with prevalent myocardial infarction and serum MCP-1 levels in the community-based Framingham Heart Study Offspring Cohort (50% women; mean age, 62 years). MCP-1 levels and CCL2 genotypes were determined in 3236 and 1797 individuals, respectively. Significant clinical correlates of MCP-1 levels were age, cigarette smoking, triglycerides, body mass index, and waist-to-hip ratio. The MCP-1-2578G allele located in the CCL2 regulatory region was significantly associated with both higher serum MCP-1 levels in a recessive genetic model (358+/-10 versus 328+/-3 pg/mL; P=0.002) and higher prevalence of myocardial infarction in a dominant genetic model (adjusted odds ratio, 2.0; 95% CI, 1.2 to 3.3; P=0.005). We also defined the linkage disequilibrium structure at the CCL2 locus and observed 6 common haplotypes in whites. We performed haplotype-based association analysis and found that only the most frequent haplotype, defined by the MCP-1-2578G allele, was associated with prevalent MI. CONCLUSIONS: Our data are consistent with the hypothesis that MCP-1 is involved in the pathogenesis of human atherosclerosis and myocardial infarction.
McDermott et al. (2005) conducted a cohort in Myocardial infarction (n=3,236). MCP-1-2578G allele (CCL2 genetic variation) vs. Absence of MCP-1-2578G allele was evaluated on Prevalent myocardial infarction (adjusted OR 2.0, 95% CI 1.2 to 3.3, p=0.005). The MCP-1-2578G allele was significantly associated with a higher prevalence of myocardial infarction (adjusted OR 2.0; 95% CI 1.2-3.3; P=0.005) and higher serum MCP-1 levels.
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