Estudo de associação genética para periodontite em indivíduos de Salvador/Ba

Abstract

INTRODUCTION: Periodontitis is an inflammatory process resulting from bacterial biofilm dysbiosis stimulated by modifiable, lifestyle-related or non-modifiable factors, which include genetic variants. OBJECTIVE: To carry out a genetic association study to identify variants associated with periodontitis in a population of Salvador. METHODOLOGY: Cross-sectional study (n = 506) developed in participants of the Asthma Control Program in Bahia, who were classified as having the presence (n = 117) or absence (n = 389) of periodontitis, according to criteria by Gomes Filho et al. (2007). Genotyping was performed using Illumina Multi-Ethnic Global Array (MEGA, Illumina), which includes more than 1.5 million variants. The studies were performed for the best fit model of the analyses, risk indicators, positive or negative association of candidate genes and a large genomic scanning study for association with periodontitis. RESULTS: The best-fit model for logistic regression included the variables age, education, obesity, mouth breathing, flossing and asthma. Obesity, no flossing and asthma are risk indicators for the development of periodontitis. The A allele at rs75985579 of the IFI16 gene is positively associated and the G allele at rs76457189 of the AIM2 gene is negatively associated with periodontitis. The interaction between these variants presented that the presence of the 2 risk alleles increases the chances of having periodontitis by more than four times compared to individuals who have 1 or none of the risk alleles (ORadjusted = 4.61; 95%CI = 1 .03 - 20.59; p-value = 0.017). In the genomic wide association study, there is a statistically significant association between rs10496038-T in RTN4 gene, rs58327429-C and rs67797971-A in LINC02505 gene and suggestive of 130 variants with the presence of periodontitis in a population of Salvador. On chromosome 2, a two-locus haplotype (rs10496038-rs74410951) belonging to the RTN4 and MTIF2 genes, respectively, has been associated with periodontitis. On chromosome 3, two two-loci haplotypes (rs74635888-rs11706761, rs114884128-rs73162961) and one five-loci haplotype (rs710479-rs710480-rs850306-rs115314220-rs9990329) have been associated with periodontitis. On chromosome 5, individuals who jointly inherit the G and C alleles of the haplotype of two loci (rs57620661-rs73054303) of the CTNND2 gene increase by 2.64 times the chances of developing periodontitis. In the interaction between genes, the heritability of 5 risk alleles or more of variants that showed high linkage disequilibrium is positively associated with more than five times the chances of an individual developing periodontitis at some point in life. These results are the basis for many other studies to confirm the association in other populations, futhermore, therapeutic targets for the treatment and control of periodontitis.