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 (<i>MMP3</i>) regulates extracellular matrix remodelling, and promoter polymorphisms may influence OSF susceptibility. This systematic review and meta-analysis evaluated the association between <i>MMP3</i> expression, promoter polymorphism, and OSF risk. Electronic databases (PubMed, Cochrane, Google Scholar, ScienceDirect) were searched for studies published between 2000 and 2023, assessing <i>MMP3</i> 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, <i>P</i> = 0.21, I² = 0%) or homozygous 6A/6A genotype (OR = 1.23, 95% CI 0.20-7.56, <i>P</i> = 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, <i>P</i> = 0.0002, I² = 0%). Egger's test indicated no publication bias. All studies demonstrated acceptable methodological quality. The <i>MMP3</i> -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 <i>MMP3</i> promoter variation in OSF pathogenesis. Larger, well-designed studies are required to validate these results and assess their diagnostic and preventive value.