Unravelling the Contribution of Matrix Metalloproteinase-3 Genotype-Phenotype to Pterygium Risk

Pterygium is a fibrovascular ocular disease characterized by extracellular matrix (ECM) remodeling. Matrix metalloproteinase-3 (MMP-3), a key ECM-modulating enzyme, has been implicated to involved in pterygium progression, but its genetic marker has never been explored. This hospital-based case-control study investigated the association between MMP-3 polymorphisms and pterygium risk in a Taiwanese cohort.

Up to five MMP-3 genotypic patterns (rs3025058, rs522616, rs591058, rs650108, and rs679620) were identified among 160 pterygium cases and 320 age- and sex-matched controls.

The MMP-3 rs3025058 5A allele was significantly associated with an elevated risk of pterygium (OR=1.94, 95%CI=1.39-2.71, p=0.0001). Compared to the wild-type 6A/6A genotype, individuals carrying MMP-3 5A/6A and 5A/5A exhibited a 1.66-fold and 4.36-fold elevated risk, respectively (p=0.0253 and 0.0014). Particularly, MMP-3 rs3025058 5A/5A genotype was significantly associated with elevated pterygium risk among elder (≥60 years old) individuals (p=0.0003). Furthermore, transcriptional and translational analyses revealed higher MMP-3 expression in carriers of the 5A allele, with the highest levels observed in 5A/5A homozygotes (all p<0.05). No significant associations were observed for the remaining four MMP-3 polymorphic variants.

MMP-3 rs3025058 may serve as a genetic biomarker for pterygium susceptibility prediction, potentially contributing to ECM dysregulation and disease progression.