Assessment of genetic effects of polymorphisms in the MCP-1 gene on serum MCP-1 levels and myocardial infarction in Japanese.
BACKGROUND
Recently, the Framingham Heart Study reported that genetic variations in CCL2 influence serum levels of monocyte chemoattractant protein-1 (MCP-1) and the incidence of myocardial infarction (MI). The purpose of the present study was to investigate the possible involvement of CCL2 in the pathogenesis of atherosclerosis and MI in Japanese.


RESULTS
Multiple regression analysis indicated that the MCP-1 levels were significantly influenced by various factors including age, body mass index, smoking, alcohol intake, high density lipoprotein-cholesterol, and systolic blood pressure. Moreover, the serum MCP-1 level was significantly correlated with intima - media thickness (p < 0.0001). However, this association disappeared when other clinical confounding factors were included in the analyses. Comprehensive analysis of common polymorphisms of CCL2 in a large community-based population and in subjects with MI found that the A(-2138)T polymorphism affected the serum MCP-1 level in a subgroup of subjects 65 years and older. However, no significant differences in the frequencies of any of the polymorphisms or haplotypes were found between subjects with and without MI. None of the polymorphisms in CCL2 affected carotid atherosclerosis.


CONCLUSIONS
The serum MCP-1 level was a good surrogate marker of atherosclerosis in the present study population. Although genetic variations in CCL2 may have some influence on MCP-1 production, their influence does not seem to contribute appreciably to atherosclerosis in Japanese. The present results did not support the recently published findings from the Framingham Heart Study. The discrepancy between the 2 studies may be related to differences in confounding factors that contribute to MCP-1 levels and in the haplotype structure of the 2 populations.
Iwai
Naoharu
N
Department of Epidemiology, National Cardiovascular Center, Suita, Japan. iwai@ri.ncvc.go.jp
Kajimoto
Kazuaki
K
Kokubo
Yoshihiro
Y
Okayama
Akira
A
Miyazaki
Shunichi
S
Nonogi
Hiroshi
H
Goto
Yoichi
Y
Tomoike
Hitonobu
H
D000368:Aged; D044466:Asian People; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D018932:Chemokine CCL2