Genetic polymorphisms and plasma levels of matrix metalloproteinases and their relationships with developing acute myocardial infarction.
OBJECTIVE
Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, plaque rupture, extracellular matrix remodeling, and myocardial infarction (MI). MMP gene polymorphisms contribute to the risk of developing cardiovascular disease. We designed to investigate the association of acute MI (AMI) with a polymorphism in the human MMP-1, 2, 3, and 9 genes in Iranian patients with AMI.


METHODS
Genomic DNA of 400 enrolled patients with AMI and 200 controls was extracted from their blood samples. The -1607 1G/2G MMP-1, -1306 C/T MMP-2, -1171 5A/6A MMP-3, -1562 C/T MMP-9 polymorphisms were detected. Plasma levels of MMPs were analyzed.


RESULTS
There are significant differences in MMP-3 '5A' allele and genotype in the patients with AMI comparing with controls. However, no significant differences were observed in MMP-1, 2, and 9 allele frequencies between the patients and controls. Differences between plasma levels of MMPs were significant in the patients than in controls. There were statistically significant differences between plasma MMP-3 in carriers of 5A allele compared with 6A allele. MMP-9 plasma levels were significantly higher in the carriers of -1306 TT and -1306 CT than CC. However, there were no statistically significant association between genetic variation of MMP-1, 2, and 3 in the patients and their plasma levels.


CONCLUSIONS
These data suggest that MMP genotyping such as genetic polymorphism in MMP-3 might be helpful in determining susceptibility to AMI in Iranian patients. In addition, susceptibility to AMI might be related to MMP-9 gene expression, which affects its plasma levels.
Ghaderian
Sayyed Mohammad Hossein
SM
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. sghaderian@yahoo.co.uk
Akbarzadeh Najar
Reza
R
Tabatabaei Panah
Akram Sadat
AS
D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran; D016015:Logistic Models; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors
D015415:Biomarkers; D020782:Matrix Metalloproteinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1