Association between matrix metalloproteinase-3 gene polymorphism and susceptibility to chronic periodontitis: A systematic review and meta-analysis

J Med Biochem. 2024 Sep 6;43(5):655-663. doi: 10.5937/jomb0-49044.

Abstract

Background: This study aimed to explore the correlation between the Matrix Metalloproteinase-3 (MMP-3) 1171 5A/6A gene polymorphism and susceptibility to Chronic Periodontitis (CP).

Methods: Following the PRISMA guidelines, a systematic search was conducted across four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) without any time or language limitations. The selection criteria included case-control studies examining the association between the MMP-3 gene polymorphism and CP. The data were independently extracted and cross-checked by two reviewers. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the studies. Statistical heterogeneity and publication bias were assessed.

Results: Five studies, published between 2004 and 2019, met the inclusion criteria for the meta-analysis. No significant association was observed between MMP-3 gene polymorphism and CP susceptibility across all subjects in the four gene models. However, subgroup analysis revealed significant differences based on genotyping methods and smoking habits. Using PCR-RFLP genotyping method, the allele and additive models showed a positive correlation with the risk of CP (5A vs 6A, OR=1.12, 95%CI (1.02č 1.23); 5A5A vs 6A6A, OR=2.85, 95%CI (1.61č4.86)). In contrast, using Sanger sequencing method, the 5A mutation appeared to reduce CP susceptibility (5A vs 6A, OR=0.77, 95%CI (0.67č0.87); 5A5A vs 6A6A, OR= 0.20, 95%CI (0.09č0.42)). Moreover, smoking habits appeared to modulate the risk. Among smokers, the 5A mutation increased susceptibility to CP, while among nonsmokers it decreased.

Conclusions: While no significant correlation was found in the overall population, the stratified analysis revealed nuanced relationships contingent on genotyping methods and smoking habits.

Uvod: Ova studija je imala za cilj da istraži korelaciju između polimorfizma gena matriks metaloproteinaze-3 (MMP-3) 1171 5A/6A i osetljivosti na hronični parodontitis (CP).

Metode: U skladu sa smernicama PRISMA, sprovedena je sistematska pretraga u četiri elektronske baze podataka (PubMed, Embase, Veb of Science i Cochrane Librari) bez ikakvih vremenskih ili jezičkih ograničenja. Kriterijumi za odabir uključivali su studije slučaja i kontrole koje su ispitivale povezanost polimorfizma gena MMP-3 i CP. Podatke su nezavisno izdvojila i unakrsno proverila dva recenzenta. Za procenu kvaliteta studija korišćena je Njukasl-Otava skala (NOS). Procenjena je statistička heterogenost i pristrasnost objavljivanja.

Rezultati: Pet studija, objavljenih između 2004. i 2019. godine, ispunilo je kriterijume za uključivanje u meta-analizu. Nije primećena značajna povezanost između polimorfizma gena MMP-3 i osetljivosti na CP kod svih subjekata u četiri genska modela. Međutim, analiza podgrupa otkrila je značajne razlike na osnovu metoda genotipizacije i navika pušenja. Koristeći metodu PCR-RFLP genotipizacije, alelni i aditivni modeli su pokazali pozitivnu korelaciju sa rizikom od CP (5A naspram 6A, OR=1,12, 95% CI (1,02č1.23); 5A5A naspram 6A6A, OR=2,85, 95% CI (1,61č4,86)). Nasuprot tome, korišćenjem Sangerove metode sekvenciranja, činilo se da mutacija 5A smanjuje osetljivost na CP (5A naspram 6A, OR=0,77, 95% CI (0,67č0,87); 5A5A naspram 6A6A, OR=0,20, 95% CI (0,09č0,42)). Štaviše, činilo se da navike pušenja moduliraju rizik. Kod pušača mutacija 5A je povećala osetljivost na CP, dok je kod nepušača smanjena.

Zaključak: Iako nije pronađena značajna korelacija u ukupnoj populaciji, stratifikovana analiza je otkrila nijansirane odnose zavisne od metoda genotipizacije i navika pušenja.

Keywords: chronic periodontitis; gene polymorphism; matrix metalloproteinase-3; meta-analysis.