Coronary artery calcification is related to functional polymorphism of matrix metalloproteinase 3: the Helsinki Sudden Death Study.
Matrix metalloproteinase 3 (MMP3) is expressed in human coronary atherosclerotic lesions and is known to be involved in degradation of the plaque and to be co-localized with calcium and fibrin deposits in advanced lesions, indicating a possible role of MMP3 in arterial calcification. The MMP3 gene promoter polymorphism leads to low promoter activity 6A6A, intermediate promoter activity 5A6A and high promoter activity 5A5A genotypes. To determine whether these genotypes predict the extent of atherosclerosis we investigated their association with different types of coronary lesions in an autopsy series of 300 middle-aged white Finnish men (aged 35-69 years) from the Helsinki Sudden Death Study (HSDS). Areas of the coronary wall covered with different atherosclerotic lesions were measured and MMP3 genotypes were determined by PCR and minisequencing. In men >/=53 years the mean area of calcified lesion in the most severely affected coronary artery was significantly associated with the MMP3 genotype (P=0.029). Subjects with high promoter activity genotypes had on average larger calcified lesion areas than those with the low-activity genotype. The MMP3 genotype (P=0.025) persisted as an independent predictor of mean calcified lesion area after stepwise adjustment for age, BMI, hypertension, diabetes, number of affected vessels and smoking. These data provide evidence that the proposed effect of MMP3 in the process of atherogenesis may be modified by the MMP3 genotype.
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, FinnMedi 2 3rd fl., PO Box 2000, FIN-33521, Tampere, Finland.
Perttu J
PJ
Pöllänen
Terho
T
Lehtimäki
Erkki
E
Ilveskoski
Jussi
J
Mikkelsson
Olli A
OA
Kajander
Pekka
P
Laippala
Markus
M
Perola
Sirkka
S
Goebeler
Antti
A
Penttilä
Kari M
KM
Mattila
Kirsi
K
Syrjäkoski
Timo
T
Koivula
Seppo T
ST
Nikkari
Pekka J
PJ
Karhunen
D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D001344:Autopsy; D001483:Base Sequence; D002114:Calcinosis / Q000473:pathology*; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology*; D016757:Death, Sudden, Cardiac / Q000473:pathology*; D005387:Finland; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D019278:Matrix Metalloproteinase 3