CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study.
BACKGROUND
Monocyte chemoattractant protein-1 (MCP-1) is a chemokine strongly implicated in promoting atherosclerosis in animal models, but human genetic evidence is contradictory.


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
David H
DH
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886, USA. dmcdermott@niaid.nih.gov
Yang
Qiong
Q
Kathiresan
Sekar
S
Cupples
L Adrienne
LA
Massaro
Joseph M
JM
Keaney
John F
JF
Larson
Martin G
MG
Vasan
Ramachandran S
RS
Hirschhorn
Joel N
JN
O'Donnell
Christopher J
CJ
Murphy
Philip M
PM
Benjamin
Emelia J
EJ
D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors
C111835:CCL2 protein, human; D018932:Chemokine CCL2