Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction.
BACKGROUND
Rupture of the fibrous cap of an atherosclerotic plaque is a key event that predisposes to acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) may contribute to weakening of the cap, which favors rupture. Stromelysin, a member of MMP family, is identified extensively in human coronary atherosclerotic lesions. It can degrade most of the constituents of extracellular matrix as well as activating other MMPs, which suggests that it may play an important role in plaque rupture. Recently, a common variant (5A/6A) in the promoter of the stromelysin gene has been identified. The 5A/6A polymorphism could regulate the transcription of the stromelysin gene in an allele-specific manner.


RESULTS
To investigate the relation between the 5A/6A polymorphism in the promoter of the stromelysin gene and AMI, we conducted a case-control study of 330 AMI patients and 330 control subjects. The prevalence of the 5A/6A+5A/5A genotype was significantly more frequent in the patients with AMI than in control subjects (48.8% vs 32.7%, P<0.0001). In logistic regression models, the odds ratio of the 5A/6A+5A/5A was 2.25 (95% CI, 1.51 to 3.35). The association of 5A/6A polymorphism with AMI was statistically significant and independent of other risk factors.


CONCLUSIONS
The 5A/6A polymorphism in the promoter of the stromelysin gene is a novel pathogenetic risk factor for AMI.
Terashima
M
M
First Department of Internal Medicine, Kobe University School of Medicine, Kobe, and Himeji Cardiovascular Center, Hyogo, Japan.
Akita
H
H
Kanazawa
K
K
Inoue
N
N
Yamada
S
S
Ito
K
K
Matsuda
Y
Y
Takai
E
E
Iwai
C
C
Kurogane
H
H
Yoshida
Y
Y
Yokoyama
M
M
D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D012421:Rupture
D019278:Matrix Metalloproteinase 3