Genetic variations of matrix metalloproteinase-1 and -3 promoter regions and their associations with susceptibility to myocardial infarction in Japanese.
Matrix metalloproteinases (MMPs) are involved in plaque rupture, which is the main pathological cause of myocardial infarction (MI). Recently, several genetic studies have demonstrated that MMP-1 1G/2G polymorphism and MMP-3 5A/6A polymorphism modify each transcriptional activity in allele specific manners. Within this context, we conducted case-control studies to examine whether these genetic polymorphisms are associated with susceptibility to MI. Two groups comprising patients with MI (group-1 164 patients, group-2 302 patients) were compared with control group comprising 335 patients without cardiovascular diseases. The MMP-3 5A allele was more frequent in patients with MI than in the control subjects (P=0.018 MI group-1, P=0.0059 MI group-2), whereas there was no disease association for MMP-1 genotypes. Logistic regression analyses revealed that MMP-3 5A/6A polymorphism was associated with susceptibility to MI [odds ratio(OR) (95% confidential interval) 1.67 (1.02-2.74); P=0.042, MI group-1; 1.61 (1.12-2.23); P=0.0095, MI group-2]. Other important findings were that there was strong linkage disequilibrium between these polymorphisms, which are located closely on chromosome 11q.22, and that the 5A-1G haplotype was a genetic risk factor for MI (OR 1.97 P=0.0082, MI group-1 OR 1.51 P=0.017, MI group-2). Taken together, the present findings suggest that genetic variations in these MMP genes and especially their haplotype may be useful genetic markers for determining susceptibility to MI in Japanese.
Nojiri
Takefumi
T
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Morita
Hiroyuki
H
Imai
Yasushi
Y
Maemura
Koji
K
Ohno
Minoru
M
Ogasawara
Ken
K
Aizawa
Tadanori
T
Saito
Akira
A
Hayashi
Doubun
D
Hirata
Yasunobu
Y
Sugiyama
Takao
T
Yamazaki
Tsutomu
T
Nagai
Ryozo
R
D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000208:ethnology* / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1