Julie T Marchesan1,2, Yizu Jiao1, Kevin Moss2, Kimon Divaris3, William Seaman4, Jennifer Webster-Cyriaque4,5, Shaoping Zhang1,2, Ning Yu6, Catharine Song1, Sompop Bencharit7, Ricardo Teles1,2, Steven Offenbacher1,2. 1. Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC. 2. General Oral Health Clinic, School of Dentistry, University of North Carolina at Chapel Hill. 3. Department of Pediatric Dentistry, School of Dentistry and Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill. 4. UNC Lineberger, School of Medicine, University of North Carolina at Chapel Hill. 5. Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill. 6. Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI. 7. Department of Prosthodontics, School of Dentistry, University of North Carolina at Chapel Hill.
Abstract
BACKGROUND: The single nucleotide polymorphism (SNP) context of a previously identified periodontitis-associated locus is investigated, and its association with microbial, biologic, and periodontal disease clinical parameters is examined. METHODS: A 200-kb spanning region of 1q12 previously highlighted in a genome-wide association scan among 4,766 European American individuals (SNP rs1633266) was annotated. Two haplotype blocks were selected. Association of these polymorphisms with data on microbial plaque composition, gingival crevicular fluid (GCF)-interleukin (IL)-1β levels, and clinical parameters of periodontal disease were examined. Descriptive analysis of IFI16 and AIM2 protein expression in gingival tissues from healthy individuals (n = 2) and individuals with chronic periodontitis (n = 2) was done via immunohistochemistry. RESULTS: The highlighted locus is a 100-kb region containing the interferon γ-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes. Two haplotype blocks, rs6940 and rs1057028, were significantly associated with increased extent bleeding on probing and levels of microorganisms Porphyromonas gingivalis, Tannerella forsythia, and Campylobacter rectus (P ≤0.05). Haplotype block rs1057028 was also significantly associated with pathogens Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans, increased GCF-IL-1β levels, and extent of probing depth ≥4 mm (P ≤0.05). Prevalence of severe periodontitis (biofilm-gingival interface P3 classification) was positively associated with haplotype block rs1057028. Similar trends were observed for haplotype block rs1057028. IFI16 and AIM2 protein expression was observed in multiple cell types of gingival tissues, including inflammatory cells. CONCLUSION: This study found IFI16 and AIM2 SNPs associated with higher levels of periodontal microorganisms and an increased percentage of periodontal disease clinical parameters, suggesting the need for functional studies and additional fine-mapping of variants in the 1q12-locus.
BACKGROUND: The single nucleotide polymorphism (SNP) context of a previously identified periodontitis-associated locus is investigated, and its association with microbial, biologic, and periodontal disease clinical parameters is examined. METHODS: A 200-kb spanning region of 1q12 previously highlighted in a genome-wide association scan among 4,766 European American individuals (SNP rs1633266) was annotated. Two haplotype blocks were selected. Association of these polymorphisms with data on microbial plaque composition, gingival crevicular fluid (GCF)-interleukin (IL)-1β levels, and clinical parameters of periodontal disease were examined. Descriptive analysis of IFI16 and AIM2 protein expression in gingival tissues from healthy individuals (n = 2) and individuals with chronic periodontitis (n = 2) was done via immunohistochemistry. RESULTS: The highlighted locus is a 100-kb region containing the interferon γ-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes. Two haplotype blocks, rs6940 and rs1057028, were significantly associated with increased extent bleeding on probing and levels of microorganisms Porphyromonas gingivalis, Tannerella forsythia, and Campylobacter rectus (P ≤0.05). Haplotype block rs1057028 was also significantly associated with pathogens Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans, increased GCF-IL-1β levels, and extent of probing depth ≥4 mm (P ≤0.05). Prevalence of severe periodontitis (biofilm-gingival interface P3 classification) was positively associated with haplotype block rs1057028. Similar trends were observed for haplotype block rs1057028. IFI16 and AIM2 protein expression was observed in multiple cell types of gingival tissues, including inflammatory cells. CONCLUSION: This study found IFI16 and AIM2 SNPs associated with higher levels of periodontal microorganisms and an increased percentage of periodontal disease clinical parameters, suggesting the need for functional studies and additional fine-mapping of variants in the 1q12-locus.
Authors: B S Michalowicz; S R Diehl; J C Gunsolley; B S Sparks; C N Brooks; T E Koertge; J V Califano; J A Burmeister; H A Schenkein Journal: J Periodontol Date: 2000-11 Impact factor: 6.993
Authors: Steven Offenbacher; Dongming Lin; Robert Strauss; Rosemary McKaig; Joanna Irving; Silvana P Barros; Kevin Moss; David A Barrow; A Hefti; James D Beck Journal: J Periodontol Date: 2006-12 Impact factor: 6.993
Authors: B S Michalowicz; D Aeppli; J G Virag; D G Klump; J E Hinrichs; N L Segal; T J Bouchard; B L Pihlstrom Journal: J Periodontol Date: 1991-05 Impact factor: 6.993
Authors: Andrew D Johnson; Robert E Handsaker; Sara L Pulit; Marcia M Nizzari; Christopher J O'Donnell; Paul I W de Bakker Journal: Bioinformatics Date: 2008-10-30 Impact factor: 6.937
Authors: S Shimizu; Y Momozawa; A Takahashi; T Nagasawa; K Ashikawa; Y Terada; Y Izumi; H Kobayashi; M Tsuji; M Kubo; Y Furuichi Journal: J Dent Res Date: 2015-02-11 Impact factor: 6.116
Authors: Cary S Agler; Kevin Moss; Kamaira H Philips; Julie T Marchesan; Miguel Simancas-Pallares; James D Beck; Kimon Divaris Journal: Adv Exp Med Biol Date: 2019 Impact factor: 2.622
Authors: Karen V Swanson; Mustafa Girnary; Tomaz Alves; Jenny Py Ting; Kimon Divaris; Jim Beck; Carolina Maschietto Pucinelli; Raquel Assed Bezerra da Silva; Dilek Uyan; Justin E Wilson; William T Seaman; Jennifer Webster-Cyriaque; Nishma Vias; Yizu Jiao; Lloyd Cantley; Arnaud Marlier; Roland R Arnold; Julie T Marchesan Journal: J Periodontol Date: 2022-06-10 Impact factor: 4.494
Authors: Julie T Marchesan; Mustafa Saadat Girnary; Kevin Moss; Eugenia Timofeev Monaghan; Grant Joseph Egnatz; Yizu Jiao; Shaoping Zhang; Jim Beck; Karen V Swanson Journal: Periodontol 2000 Date: 2020-02 Impact factor: 7.589