MMP-3-1612 polymorphism - a risk factor for deep venous thrombosis formation

Abstract

Summary: Background:We investigated the association of the 5A/6A polymorphism in the promoter region at -1612 of the matrix metalloproteinase-3 gene (MMP-3-1612) and deep venous thrombosis (DVT). Patients, materials and methods: The distribution of the MMP-3 (-1612 5A/6A) polymorphism in the case and control groups was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum MMP-3 level of two groups was detected using enzyme-linked immunosorbent assay (ELISA). HepG2 cells containing MMP-3-1612 recombinant plasmid were cultured in vitro and the MMP-3 level was defined by luminescence intensity of luciferase. A DVT rat model was built. Serum MMP-3 level in the rats' wounded vein at different time points was detected by ELISA and recorded for investigation of the association between MMP-3 and DVT. Statistical data analysis was conducted with SPSS18.0. Results: On the basis of the observation of MMP-3-1612 genotype frequency and allele frequency in the case and control groups, we identified significantly higher MMP-3-1612 5A allele frequency and higher serum MMP-3 level in the case group than in the control group (both P < 0.05). According to in vitro luciferase measurements, the 5A allele had higher transcriptional activity than the 6A allele. As observed in the rat model, serum MMP-3 level increased with time passing and thrombosis formation after modelling. Conclusions: The MMP-3-1612 5A/6A polymorphism may effect serum MMP-3 level and over-expression of serum MMP-3 level may be a risk factor for DVT formation.

Association of Matrix Metalloproteinase (MMP) Gene Polymorphisms With Knee Osteoarthritis: A Review of the Literature

“…MMP-3 gene expression is primarily regulated during translation from various stimuli such as growth factors and cytokines. The -1612 5A/6A SNP is an MMP-3 gene polymorphism that has been associated with deep venous thrombosis [ 37 ] and coronary artery disease [ 38 ]; however, this SNP has not been associated with knee OA in a Thai population [ 13 ]. A weak association of the minor G allele of rs650108 with knee OA risk in a recessive model [ 17 ] has been detected in a Chinese population.…”