Matrix metalloproteinases-3 gene-promoter polymorphism as a risk factor in oral submucous fibrosis: A systematic review and meta-analysis.

Oral submucous fibrosis (OSF) is a progressive potentially malignant disorder. Matrix metalloproteinase-3 (MMP3) regulates extracellular matrix remodelling, and promoter polymorphisms may influence OSF susceptibility. This systematic review and meta-analysis evaluated the association between MMP3 expression, promoter polymorphism, and OSF risk. Electronic databases (PubMed, Cochrane, Google Scholar, ScienceDirect) were searched for studies published between 2000 and 2023, assessing MMP3 expression or promoter polymorphism in OSF. Four eligible studies were analysed using RevMan 5.4. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using I² statistics, and publication bias using funnel plot asymmetry and Egger's test. No significant association was observed between OSF risk and the homozygous 5A/5A genotype (OR = 2.34, 95% CI 0.63-8.71, P = 0.21, I² = 0%) or homozygous 6A/6A genotype (OR = 1.23, 95% CI 0.20-7.56, P = 0.83, I² = 89%). The heterozygous 5A/6A genotype showed a significant association with increased OSF susceptibility (OR = 2.75, 95% CI 1.63-4.64, P = 0.0002, I² = 0%). Egger's test indicated no publication bias. All studies demonstrated acceptable methodological quality. The MMP3 -1171 5A/6A promoter polymorphism is significantly associated with nearly three-fold increased OSF risk, whereas homozygous genotypes show no significant association. These findings suggest a role of MMP3 promoter variation in OSF pathogenesis. Larger, well-designed studies are required to validate these results and assess their diagnostic and preventive value.