Validation in a Brazilian population of gene markers of periodontitis previously investigated by GWAS and bioinformatic studies

Abstract

Background: Bioinformatic tools and genome-wide association studies (GWAS) have led to comprehensive identification of single nucleotide polymorphisms (SNPs) associated with periodontitis in diverse populations. Here we aimed to detect and validate the association of seven SNPs as genetic markers of susceptibility to periodontitis in a Brazilian population. Methods: This case-control study assessed complete periodontal parameters of 714 subjects with periodontal status classified as healthy/mild periodontitis (n = 356) and moderate/severe periodontitis (n = 358). Genotyping for rs187238, rs352140, rs1360573, rs2521634, rs3811046, rs3826782, and rs7762544 SNPs were evaluated. Genetic-phenotype associations, and sex or smoking effects of SNPs on periodontitis were tested using multiple logistic regressions adjusted for covariates. Results: The rs2521634-AA (close to NPY gene) presented increased risk for severe periodontitis (OR = 2.34; 95% CI = 1.19-4.59). The rs3811046-GG (IL37 gene) demonstrated increased risk for moderate periodontitis (OR = 2.58; 95% CI = 1.28-5.18). Higher risk for moderate periodontitis was found in male with rs7762544-AG close to NCR2 gene. The rs352140-TT in the TLR9 gene proved to be associated with lower risk to severe periodontitis in men. The rs2521634-AA was associated with higher percentage of interproximal probing pocket depth (P = .004).Conclusions: This is the first evidence of validation in a Brazilian population of genetic markers of periodontitis previously investigated by GWAS and bioinformatics studies. SNPs in the NPY, IL37, and NCR2 genes were associated with susceptibility to moderate or severe periodontitis; whereas the TLR9 marker was associated with lower chance to develop severe periodontitis. Those SNPs had sex-and smoking-habit-specific effects on periodontitis; reinforcing the genetic profile predisposing to periodontitis.

Interleukin-37 gene polymorphism and susceptibility to coronavirus disease 19 among Iraqi patients

“…In the first, rs3811046 was linked with severe chronic periodontitis (OR = 1.50), 10-year incident tooth loss (relative risk = 1.33) and aggressive periodontitis (OR = 1.12) in German/Dutch adults (Offenbacher et al, 2018). In a more recent study, it has been demonstrated that rs3811046 was associated with an increased risk of developing moderate periodontitis (OR = 2.58) in a Brazilian population (Cirelli et al, 2021). In Graves' disease, the rs3811046 variant was significantly associated with a decreased risk in female patients (OR = 0.777) (Yan et al, 2015).…”

Evidence Linking PPARG Genetic Variants with Periodontitis and Type 2 Diabetes Mellitus in a Brazilian Population

“…We used the answers to classify them as never-smokers or ever-smokers (current smokers + former smokers). Regarding smoking status, participants were classified as a smoker when they reported smoking on a daily basis for at least one year with a mean of 20 cigarettes per day, and a former smoker when they had stopped smoking for at least one year [ 16 , 51 ]. Each participant also self-reported their skin color, as white (67.4%), black (10.83%), brown (19.31%) or mulatto (2.46%).…”

“…Each participant also self-reported their skin color, as white (67.4%), black (10.83%), brown (19.31%) or mulatto (2.46%). We assessed the clinical periodontal parameters—interproximal probing pocket depth (PPDi), interproximal clinical attachment level (CALi), bleeding on probing (BOP), the visible plaque index, and marginal bleeding—by utilizing a University of North Carolina-15 periodontal probe at four sites (interproximal sites) around each tooth [ 16 , 17 , 51 ]. We followed the Centers for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP) criteria to define periodontitis [ 52 ].…”

“…Based on the periodontal status and glycemic profile of each individual, we divided the subjects into three groups: 345 individuals with healthy periodontium or mild periodontitis and without T2DM (the Healthy group); 349 individuals with moderate or severe periodontitis and without T2DM (the Periodontitis group); and 202 individuals with moderate or severe periodontitis as well as T2DM (P + T2DM group). The inclusion and exclusion criteria have been described in previous studies [ 16 , 17 , 51 ].…”

Polymorphisms in Genes of Lipid Metabolism Are Associated with Type 2 Diabetes Mellitus and Periodontitis, as Comorbidities, and with the Subjects’ Periodontal, Glycemic, and Lipid Profiles

“…A complete periodontal examination of all subjects assessed the following clinical signs and parameters at four interproximal sites around each tooth: probing pocket depth (PPDi) and clinical attachment level (CALi), measured to the nearest millimeter by a UNC-15 periodontal probe (Millennium®) and the presence of visible plaque, marginal bleeding and bleeding on probing (BOP) [ 32 , 33 ]. The last three parameters were registered as a percentage of the total number of interproximal sites assessed.…”