Matrix metalloproteinase gene polymorphisms in patients with coronary artery disease

Abstract

Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of atherosclerosis, the pathology underlying the majority of coronary artery disease (CAD). In this study we tested the hypothesis that polymorphic variation in the MMP genes influences the risk of developing atherosclerosis. We analyzed functional polymorphisms in the promoter of the MMP-1, MMP-3, MMP-9 and MMP-12 genes in 183 Brazilian Caucasian individuals submitted to coronary angiography, of which 67 (37%) had normal coronary arteries (control group) and 116 (63%) had CAD (CAD patient group). The -1607 1G/2G MMP-1, -1171 5A/6A MMP-3, -1562 C/T MMP-9, -82 A/G MMP-12 polymorphisms were analyzed by PCR followed by restriction digestion. No significant differences were observed in allele frequencies between the CAD patients and controls. Haplotype analysis showed no differences between the CAD patients and controls. There was a significant difference in the severity of CAD, as assessed by the number of diseased vessels, in MMP-1 1G/1G homozygous individuals and in those homozygous for the 6A allele of the MMP-3 polymorphism. However, multivariate analysis showed that diabetes mellitus was the only variable independently associated with CAD severity. Our findings indicated that MMP polymorphisms have no significant impact on the risk and severity of CAD.

Matrix metalloproteinase family gene polymorphisms and risk for coronary artery disease: systematic review and meta-analysis

“…Out of 59 qualified studies, 28 studies included Caucasians,8 10 18 20 24 27–29 32 35 37 39 41 43–45 49–51 55 56 21 studies included East Asians,11 17 21 22 25 26 31 33 34 38 42 47 48 53 54 57–59 eight studies included Middle Easterns,9 15 16 23 30 40 46 and two studies included mixed populations 19 36. There were 15 studies involving patients and controls matched on age 9 15 16 29 33 36 39 44 48 56 58.…”

Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population

“…A major contribution of a single gene is very unlikely in multifactorial diseases such as atherosclerosis, where a large number of pathogenetic mechanisms lead to a clinical outcome ( Dalepiane et al , 2007 ). Thus effects of a loss-of-function polymorphism alone are probably not sufficient to influence the progression of atherosclerosis, but the accumulation of “unfavorable” oxidative stress-associated gene polymorphisms is likely associated with the evolution of its clinical manifestations ( Katakami et al , 2009 ).…”

Association Between High Serum Matrix Metalloproteinase-9 and MMP-9 (-1562C>T) Polymorphism in Patients With ST-Elevation Acute Myocardial Infarction

“…Despite several evidences of the role of MMP-9 polymorphism in coronary artery disease, some publications indicated conflicting conclusions regarding role of MMP-9 polymorphism in severity of coronary artery disease [ 9 , 19 , 20 ]. These similarities and differences in the results of previous studies possibly because of polymorphism that occurs in the promoter region will affect gene transcription and increase expression of MMP-9 [ 21 ].…”