Genetic variations of matrix metalloproteinase-1 and -3 promoter regions and their associations with susceptibility to myocardial infarction in Japanese
| Autor: | Koji Maemura, Tsutomu Yamazaki, Tadanori Aizawa, Takao Sugiyama, Doubun Hayashi, Yasunobu Hirata, Ryozo Nagai, Ken Ogasawara, Minoru Ohno, Akira Saito, Yasushi Imai, Hiroyuki Morita, Takefumi Nojiri |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Oncology Linkage disequilibrium medicine.medical_specialty Myocardial Infarction Linkage Disequilibrium Genetic determinism Asian People Japan Internal medicine Genetic variation Genotype medicine Humans Genetic Predisposition to Disease Allele Promoter Regions Genetic Aged Polymorphism Genetic business.industry Chromosomes Human Pair 11 Haplotype Genetic Variation Odds ratio Middle Aged Surgery Logistic Models Genetic marker Case-Control Studies Female Matrix Metalloproteinase 3 Matrix Metalloproteinase 1 Cardiology and Cardiovascular Medicine business |
| Zdroj: | International Journal of Cardiology. 92:181-186 |
| ISSN: | 0167-5273 |
| DOI: | 10.1016/s0167-5273(03)00100-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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