Associação de variantes genéticas do gene NELL1 com a presença da periodontite

Abstract

Introduction: Periodontitis is an inflammatory disease due to complex interactions between a dysbiotic oral microbiota and the host's immune response. Genetic, environmental, and systemic aspects may be associated with periodontitis. Candidate gene studies and genome-wide association studies (GWAS) seek to identify correlations between variants in genes and periodontitis. The NELL1 gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats and its genetic variants may be involved in the regulation of differentiation and cell growth, related to the encoded NELL-1 protein. Purpose: Investigate the association between genetic variants of the NELL1 gene and periodontitis. Materials and Methods: A cross-sectional study was carried out with 506 unrelated adult individuals, classified as having the presence (n=117) or absence (n=389) of periodontitis, recruited through the Program for Asthma Control in Bahia (ProAR). Through a questionnaire and an interview, pieces of information were obtained about sociodemographic characteristics, habits and lifestyle, and medical and dental history. After the oral examination, individuals with at least 4 teeth with at least 1 site with a probing depth ≥ 4 mm, clinical attachment level ≥ 3 mm, and bleeding upon stimulation in the same location were classified as periodontitis. Genotyping was performed using the Illumina Infinium Multi-Ethnic kit. The association analysis was carried out in the Plink 1.9 software using multivariate logistic regression adjusted for age greater than or equal to 40 years, obesity, mouth breathing habits, use of dental floss, asthma, and ancestry. Results: Twenty-five variants of the NELL1 single nucleotide (SNV) gene were positively associated with periodontitis and 14 variants were negatively associated. Correlations referring to age, obesity, mouth breathing habits, dental flossing, and asthma were observed. The alleles of the variants rs10766721-A, rs74326837-A, and rs76391583-G were positively related to periodontitis. Variants rs6483735-A, rs919476-A, rs111375391-G were positively associated with periodontitis. The C allele of rs10766743 was negatively associated with periodontitis. In the rs34835859 variant, individuals with the C/A genotype in the additive model, who use dental floss, are 2.45 times more likely to develop periodontitis, (OR = 2.45; 95% CI = 1.17-5, 12; p-value = 0.026). People aged 40 years or older, with the G/G genotype in the rs7130084 variant, are 2.88 times more likely to develop periodontitis (OR = 2.88; 95% CI = 1.35 – 6.13; value p = 0.035) than people with the same genotype and age greater than or equal to 40 years. Conclusion: In this study, variants of the NELL1 gene were associated with periodontitis. In the gene-environment analysis, the covariates obesity, lack of flossing use, presence of asthma, and age greater than or equal to 40 years are linked to variants associated with the development of periodontitis. Future prospective studies should be carried out to test the hypothesis of the influence and functionality of these variants described in the present study.