Introduction: Erosive tooth wear (ETW) is a multifactorial condition of increasing prevalence in the younger population. This study aimed to explore the association between different ETW phenotypes with MMP2 and COMT single-nucleotide variants and selected environmental factors. Methods: Saliva samples, erosive wear, and dental caries experience data and dietary/behavioral information from 16- to 18-year-old patients (n = 747) were used. Genotypes were obtained, and phenotypes were further analyzed considering diet and behavioral data, using logistic regression as implemented in PLINK, with an alpha of 0.05. Results: When comparing individuals’ ETW-free with those with mild ETW, an association was found with COMT rs6269 (p = 0.02). The comparison between ETW-free individuals with individuals with severe ETW also showed an association with COMT rs6269 under the recessive model (p = 0.03). Logistic regression showed that in the presence of less common alleles of MMP2 rs9923304 and COMT rs6269, ETW was more likely to occur when individuals drank wine. The GG genotype of COMT rs6269 was associated with the presence of lower (p = 0.02) and higher (p = 0.02) caries experience when individuals with ETW only in enamel were compared with individuals with ETW involving dentin. Conclusion: The results support a role of genes in ETW, with wine consumption being identified as a significant modulator, suggesting that gene-environment interactions may contribute to the development of ETW.

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