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

Author(s)

Cirelli, Thamiris ^{[1, 2]} ; Nepomuceno, Rafael ^{[1, 2]} ; Orrico, Silvana R. P. ^{[1, 3]} ; Rossa, Jr., Carlos ^[1] ; Cirelli, Joni A. ^[1] ; North, Kari E. ^{[4, 5]} ; Graff, Mariaelisa ^{[4, 6]} ; Barros, Silvana P. ^[7] ; Scarel-Caminaga, Raquel M. ^[2]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Dent Araraquara, Dept Diag & Surg, Araraquara, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Dent Araraquara, Dept Morphol Genet Orthodont & Pediat Dent, Araraquara, SP - Brazil

^[3] Union Coll Great Lakes UNILAGO, Adv Res Ctr Med, Sao Jose Do Rio Preto, SP - Brazil

^[4] Univ North Carolina Chapel Hill UNC, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC - USA

^[5] Univ North Carolina Chapel Hill UNC, Carolina Populat Ctr, Chapel Hill, NC - USA

^[6] Univ North Carolina Chapel Hill UNC, Sch Publ Hlth, Carolina Ctr Genome Sci, Chapel Hill, NC - USA

^[7] Univ North Carolina Chapel Hill UNC, Sch Dent, Dept Comprehens Oral Hlth Periodontol, Chapel Hill, NC - USA

• Document type: Journal article
• Source: Journal of Periodontology; v. 92, n. 5, p. 689-703, MAY 2021.
• Web of Science Citations: 1

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 toNPYgene) presented increased risk for severe periodontitis (OR = 2.34; 95% CI = 1.19-4.59). The rs3811046-GG (IL37gene) 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 toNCR2gene. The rs352140-TT in theTLR9gene 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 theNPY, IL37, andNCR2genes were associated with susceptibility to moderate or severe periodontitis; whereas theTLR9marker 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. (AU)

• FAPESP's process: 16/03753-8 - Investigation of potential genetic markers of chronic periodontitis associated or not with type 2 diabetes mellitus through patient's genetic susceptibility and both glycemic and lipid profiles
• Grantee: Raquel Mantuaneli Scarel Caminaga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/18313-3 - Investigation of genetic variations susceptibility to chronic periodontitis by OpenArray®: Biostatistics, Bioinformatics and Functional Analysis
• Grantee: Rafael Nepomuceno Oliveira
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 14/13295-1 - Investigation of the association of genetic variation regarding susceptibility to chronic periodontal disease by OpenArray
• Grantee: Rafael Nepomuceno Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate