Relationship of the metalloproteinase -3 and Peptidyl Arginine Deiminase-4 polymorphisms with rheumatoid arthritis and osteoarthritis

ABSTRACTObjective: The destruction of cartilage and bone in rheumatoid arthritis is mediated by proteolytic enzymes that are secreted by an inflammatory synovial tissue. Since destructive enzymes of the matrix metalloproteinase (MMP) family are involved in this process, allelic polymorphisms of MMP genes could possibly influence the course of RA. The abnormal expression or activation of PADI4 in RA synovium is suggested to be responsible for the high level of citrullinated peptide in RA plasma. OA is one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints. Proteinases like matrix metalloproteinases and aggrecanases have now been proven to be the principal initiators of OA progression. The present study aimed to explain the pathogenesis of joint degeneration in rheumatoid arthritis and osteoarthritis as an example of collagen diseases via two mechanisms immunogenic and proteolytic and to evaluate and compare the roles of (MMP3) & (PADI4) polymorphism in development of rheumatoid arthritis and osteoarthritis.Subjects& Methods: The study group included 50 patients with rheumatoid arthritis and osteoarthritis and 25 healthy controls. MMP3 gene polymorphism at5A/6A promoter at position -1171 and PADI-4(96) gene polymorphism were identified by PCR-based restriction fragment length polymorphism (RFLP), while serum MMP3 concentration was determined by ELISA.Results: As regards mmp3 polymorphism: In the 25 rheumatoid arthritis patients, the homozygous 5A/5A was found in 4 patients (16%), the heterozygous 5A/6A in 13 patients (52)% , and the homozygous abnormal 6A/6A in 8patients (32%). In osteoarthritis group, 6 persons (24%) had homozygous 5A/5A, and 13 persons (52%) had heterozygous 5A/6A and 6 persons (24%) had homozygous abnormal 6A/6A. There was a significant association of MMP3 variant in RA and OA when compared with the control group (p=0.008 and p= 0.027 respectively). There is significant association between genotype variants of MMP3 with severity in osteoarthritis group (P=0.001). There is significant association between genotype variants of MMP-3 with RF and severity in rheumatoid arthritis group (P=0.02, 0.009respectively).MMP3 concentration showed that the mean values for the MMP3 concentration in the sera were 31.08  16.9 ng/ml in control group, 38.24 24.4 ng/ml in RA group and 40.08 19.16ng/ml in OA group, there was non significant association when compared with the control group (P=0.3).Also there is non significant association between MMP-3 concentrations with MMP-3 genotypes.