Coronary artery complicated lesion area is related to functional polymorphism of matrix metalloproteinase 9 gene - An autopsy study

Matrix metalloproteinase 9 (MMP9) is expressed in human atherosclerotic pla ques, and the protein is localized in human coronary atherosclerotic lesion s. The MMP9 gene has a C-to-T promoter polymorphism at position -1562, whic h affects transcription and leads to promoter low-activity (C/C) and high-a ctivity (C/T, T/T) genotypes. To determine whether these genotypes exert an influence on the atherosclerotic lesion area, we investigated their associ ation with different types of coronary lesions in an autopsy cohort of 276 men aged 33 to 69 years. Areas of the coronary wall covered with fatty stre aks and fibrotic, calcified, and complicated lesions were measured, and the percentage of coronary narrowing was determined. MMP9 genotypes were deter mined by polymerase chain reaction and restriction enzyme digestion. In men aged greater than or equal to 53 years, the mean area of complicated lesio ns in 3 coronaries was significantly associated with the MAIN genotype (P=0 .008). Subjects with high promoter activity genotypes had, on average, larg er complicated lesion areas than did those with the low-activity genotype. The MMP9 genotype persisted as an independent predictor of complicated lesi on area after adjustment for age, body mass index, hypertension, diabetes, and smoking (P=0.012). These data provide evidence that the proposed effect of MMP9 in the process of atherosclerotic lesion development may be modifi ed by the MMP9 genotype.