Association between multiple genetic polymorphisms and molar-incisor hypomineralization: a population-based study

Luíse Gomes-Souza; Aluhê Lopes Fatturi; Rafaela Scariot; Cleber Machado-Souza; Erika Calvano Küchler; João Armando Brancher; Juliana Feltrin-Souza

doi:10.1590/1678-7757-2025-0074

Authors

Luíse Gomes-Souza Universidade Federal do Paraná, Departamento de Estomatologia, Curitiba, PR https://orcid.org/0000-0002-4467-0562
Aluhê Lopes Fatturi Universidade Federal do Paraná, Departamento de Estomatologia, Curitiba, PR https://orcid.org/0000-0002-8910-4417
Rafaela Scariot Universidade Federal do Paraná, Departamento de Estomatologia, Curitiba, PR https://orcid.org/0000-0002-4911-6413
Cleber Machado-Souza Colégio Pequeno Principe, Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR
Erika Calvano Küchler University Hospital Bonn, Medical Faculty, Department of Orthodontics, Bonn
João Armando Brancher Universidade Positivo, Escola de Ciências da Saúde, Curitiba, PR https://orcid.org/0000-0002-8914-702X
Juliana Feltrin-Souza Universidade Federal do Paraná, Departamento de Estomatologia, Curitiba, PR https://orcid.org/0000-0001-9969-3721

DOI:

https://doi.org/10.1590/1678-7757-2025-0074

Keywords:

Dental enamel, Molar hypomineralization, Genetic polymorphism, Estrogen receptor, Vitamin D Receptor

Abstract

Background Certain genes present variants associated with molar-incisor hypomineralization (MIH) pathogenesis, especially genes encoding enamel development proteins related to morphogenesis, immune response, and hormone transcription and reception, demonstrating that MIH is likely a gene-environment issue with multiple genes having small individual effects. Objective To evaluate the association between single nucleotide polymorphisms (SNPs) and MIH. Methodology A sample of 90 children with MIH and 262 children without MIH were included in this study. Calibrated examiners diagnosed MIH (Kappa≥0.75) using the European Academy of Paediatric Dentistry (EAPD) criteria and modified DDE index in clinical exams. SNPs in the IL-6 (rs2069840 and rs2069833), ESR (rs9340799, rs1256049, rs4986938, and rs2234693), VDR (rs739837 and rs2228570), and 5-HTT genes (rs1042173 and rs38133034) were genotyped by real-time polymerase chain reaction from oral mucosa cells collected. Associations between MIH and SNPs genotypes (recessive and dominant models) and allele frequencies were tested using the chi-square test. Odds ratio (OR) and confidence intervals (CI) were calculated. A significance level of 5% was adopted. Genotypes were tested by the Hardy–Weinberg Equilibrium using chi-square. Results In rs4986938 (ESR2 gene), children with CT/TT presented significantly lower odds of MIH than CC (OR=0.57, CI 95% [0.35-0.92]). There was no significant association between MIH and other evaluated genes. Conclusion The genetic polymorphism in the ESR gene is associated with MIH, suggesting that MIH etiology presents a polygenetic involvement.

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