Functional promoter polymorphism of matrix metalloproteinase (MMP)-3 5A/6A and its interaction with MMP-7 A-181G polymorphism in multiple sclerosis

Multiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system (CNS) in which demyelination, axonal inflammation and damage occurs. The aim of present study was to investigate the influence of matrix metalloproteinase (MMP)-3 5A/6A and its interaction with MMP-7 A-181G polymorphism on the risk and the clinical course of MS. We studied 121 patients and 106 healthy individuals without family history of MS or any other autoimmune diseases from Kermanshah province. The MMP-3 and MMP-7 genotypes were detected using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The MMP-3 6A allele was more prevalent in patients (70.2%) than that in the controls (67%, p=0.45). The frequency of MMP3 6A/6A genotype was higher in secondary progressive-MS (SP-MS) patients (57.9%) than that of relapsing remitting-MS (RR-MS) patients (39.2%) but it did not reach to a statistical significance. The concomitant presence of both MMP-3 6A and MMP-7 -181 G alleles compared to the combined presence of MMP-3 6A and MMP-7 -181A alleles increased the risk of MS by 1.64-fold (p=0.05). In conclusion, our study for the first time among a homogenous ethnic group of Iranians (Kurds) indicated the absence of an influence of MMP-3 5A/6A polymorphism on the risk of MS or its clinical course. However, we detected a gene-gene interaction between MMP-3 and MMP-7 that increased the risk of MS in the presence of MMP-3 6A and MMP-7 -181 G alleles.