Evaluation of MMP-8 and MMP-9 Gene Variants and Their Association with Orthodontically Induced External Apical Root Resorption

Abstract

Background: Orthodontically induced external apical root resorption (EARR) is a multifactorial adverse effect of orthodontic tooth movement, with evidence supporting contributions from treatment-related and host genetic factors. Objective: To examine the simulated association of MMP-8 and MMP-9 genotype categories with EARR while accounting for age, sex, and treatment duration.
Methods: A synthetic dataset of 400 participants was analyzed, comprising 160 EARR and 240 non-EARR records. Genotype distributions were compared using chi-square tests, crude odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and multivariable binary logistic regression was performed. Results: EARR records had longer simulated treatment duration than non-EARR records (24.52 ± 4.59 vs 21.67 ± 4.52 months; p<0.001). MMP-8 genotype distribution differed between groups (χ²=12.13, p=0.002), as did MMP-9 genotype distribution (χ²=15.97, p<0.001). Relative to AA, MMP-8 GG showed a crude OR of 2.74 (95% CI 1.54–4.88), while relative to CC, MMP-9 TT showed an OR of 3.17 (95% CI 1.78–5.65). In multivariable analysis, MMP-8 GG (adjusted OR 2.30, 95% CI 1.24–4.28), MMP-9 TT (adjusted OR 2.85, 95% CI 1.54–5.27), male sex (adjusted OR 2.02, 95% CI 1.30–3.14), and treatment duration (adjusted OR 1.14 per month, 95% CI 1.08–1.20) were independently associated with simulated EARR. Conclusion: The simulated dataset demonstrates a genotype-associated pattern involving MMP-8 and MMP-9 alongside treatment duration. These results are hypothesis-generating only and require validation in a prospectively collected, ethically approved clinical cohort.