PMID- 16116069
OWN - NLM
STAT- MEDLINE
DCOM- 20060215
LR  - 20220408
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 112
IP  - 8
DP  - 2005 Aug 23
TI  - CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 
      levels and myocardial infarction in the Framingham Heart Study.
PG  - 1113-20
AB  - 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.
FAU - McDermott, David H
AU  - McDermott DH
AD  - National Institute of Allergy and Infectious Diseases, National Institutes of 
      Health, Bethesda, MD 20892-1886, USA. dmcdermott@niaid.nih.gov
FAU - Yang, Qiong
AU  - Yang Q
FAU - Kathiresan, Sekar
AU  - Kathiresan S
FAU - Cupples, L Adrienne
AU  - Cupples LA
FAU - Massaro, Joseph M
AU  - Massaro JM
FAU - Keaney, John F Jr
AU  - Keaney JF Jr
FAU - Larson, Martin G
AU  - Larson MG
FAU - Vasan, Ramachandran S
AU  - Vasan RS
FAU - Hirschhorn, Joel N
AU  - Hirschhorn JN
FAU - O'Donnell, Christopher J
AU  - O'Donnell CJ
FAU - Murphy, Philip M
AU  - Murphy PM
FAU - Benjamin, Emelia J
AU  - Benjamin EJ
LA  - eng
GR  - N01-HC 25195/HC/NHLBI NIH HHS/United States
GR  - R01 HL-076784/HL/NHLBI NIH HHS/United States
GR  - R01 HL-64753/HL/NHLBI NIH HHS/United States
GR  - U01 HL-66582/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Aged
MH  - Chemokine CCL2/*blood/*genetics
MH  - Cohort Studies
MH  - Female
MH  - Genetic Predisposition to Disease/epidemiology
MH  - Haplotypes
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Massachusetts/epidemiology
MH  - Middle Aged
MH  - Myocardial Infarction/*blood/epidemiology/*genetics
MH  - Polymorphism, Genetic
MH  - Prevalence
MH  - Risk Factors
EDAT- 2005/08/24 09:00
MHDA- 2006/02/16 09:00
CRDT- 2005/08/24 09:00
PHST- 2005/08/24 09:00 [pubmed]
PHST- 2006/02/16 09:00 [medline]
PHST- 2005/08/24 09:00 [entrez]
AID - 112/8/1113 [pii]
AID - 10.1161/CIRCULATIONAHA.105.543579 [doi]
PST - ppublish
SO  - Circulation. 2005 Aug 23;112(8):1113-20. doi: 10.1161/CIRCULATIONAHA.105.543579.