Abstract / Summary
Background/Objectives: Matrix metalloproteinases (MMPs) are enzymes that play a key role in the disruption of blood–brain barrier integrity and neuroinflammatory processes. The objective of this study is to elucidate the contribution of Matrix Metalloproteinase 1 (MMP1) rs1799750 (−1607 1G/2G), Matrix Metalloproteinase 2 (MMP2) [rs243865 (−1306 C > T), rs2285053 (−735 C > T)], and Matrix Metalloproteinase 3 (MMP3) rs3025058 (−1171 5A/6A) genetic variants to the pathogenesis of multiple sclerosis (MS), and to evaluate their potential as genetic markers of neurodegeneration in conjunction with clinical and environmental factors. Methods: The study included 100 MS patients and 100 healthy controls. Genotype distributions of MMP1, MMP2, and MMP3 genetic variants were determined using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. Participants’ demographic data and clinical histories were recorded. The relevant MMP loci were genotyped, and genotype–allele frequencies as well as haplotype combinations were evaluated. Their associations with clinical parameters were analyzed using Chi-square tests, Odds Ratios (ORs), and One-Way Analysis of Variance (One-Way ANOVA). Results: The rates of heart disease history (13% vs. 4%, p = 0.031), alcohol consumption (29% vs. 14%, p = 0.011), and smoking (35% vs. 21%, p = 0.029) were significantly higher in MS patients compared to the control group. The MMP2 rs243865 (−1306) TT genotype showed a strong positive association with MS, exhibiting approximately 10-fold higher odds of the disease (p < 0.001). Similarly, the MMP3 rs3025058 5A/6A genotype was associated with 2.45-fold higher odds of MS (p < 0.003). Higher odds of the disease were particularly evident with the MMP2 rs243865 (−1306) TT and MMP3 rs3025058 6A/6A combination (OR: 6.769, p < 0.001), followed by the MMP2 rs243865 (−1306) TT and MMP2 rs2285053 (−735) CT combination (OR: 7.169, p < 0.001). No statistically significant association was found between the examined genotypes or haplotypes and clinical parameters, including attack frequency and disease duration (p > 0.05). Conclusions: Our study indicates that MMP2 and MMP3 genetic variants are significantly associated with MS susceptibility, though these variants do not appear to directly influence disease severity parameters such as attack frequency and disease duration. These findings further support the potential involvement of MMPs, particularly in the immunopathological phase of the disease. Consequently, addressing modifiable lifestyle factors in individuals carrying susceptibility-associated genetic profiles and considering early interventions targeting MMP pathways may offer valuable strategic insights for personalized MS management. The data obtained suggest that MMP variations have a potential to be not merely disease markers, but also early-stage therapeutic markers that may be addressed before the first clinical attack occurs. The present study also emphasizes the necessity of transitioning from a reactive approach to a proactive, genetically based personalized medicine paradigm in MS management.