title: Genetic variations of matrix metalloproteinase-1 and -3 promoter regions and their associations with susceptibility to myocardial infarction in Japanese.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Nojiri
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.forename: Koji
authors.initials: K
authors.lastname: Maemura
authors.forename: Minoru
authors.initials: M
authors.lastname: Ohno
authors.forename: Ken
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Tadanori
authors.initials: T
authors.lastname: Aizawa
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.forename: Doubun
authors.initials: D
authors.lastname: Hayashi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: 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
chemical_list: D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1