Association of MMP9 polymorphism rs3918242 with clinical findings in Slovak multiple sclerosis patients

OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease affecting mostly young people. Matrix metalloproteinases (MMPs) are zinc-dependent proteases, which can be involved in neuroinflammation. In the brain MMPs are engaged in the cleavage of the blood brain barrier resulting in the migration of autoreactive T cells into the CNS. The aim of the study was to analyse the association of MMP9 gene polymorphism rs3918242 (-1562C/T) with susceptibility to MS and to evaluate its influence on the age at disease onset, neurological disability (EDSS), severity (MSSS) and progression index (PI). METHODS: 217 MS patients and 243 control subjects from Slovakia were genotyped for MMP9 polymorphism rs3918242. The same individuals were genotyped also for the HLA-DRB1*15:01 allele as a known genetic risk factor for MS development. The analysis was performed by PCR-RFLP method. RESULTS: No statistically significant differences in either MMP9 allele or genotype frequencies at -1562C/T between MS patients and control group have been observed (p> 0.05). Nevertheless, correlation of clinical findings with MMP9 genotypes revealed significant association in the HLA-DRB 1*15:01 negative MS patients indicated that CT carriers tend to have significantly higher EDSS and MSSS score as compared to other MMP9 genotype carriers (p=0.02-0.04). CONCLUSION: Genetic predisposition of MMP9 at -1562C/T to MS development in Slovak patients was examined for the first time. Association between CT carriers and higher EDSS and MSSS score was found in the HLA-DRB1*15:01 negative MS patients suggesting that MMP9 polymorphism may modify the MS disability and severity status.