title: Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.|General Oral Health Clinic, School of Dentistry, University of North Carolina at Chapel Hill.
authors.forename: Julie T
authors.initials: JT
authors.lastname: Marchesan
authors.affiliation: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Yizu
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: General Oral Health Clinic, School of Dentistry, University of North Carolina at Chapel Hill.
authors.forename: Kevin
authors.initials: K
authors.lastname: Moss
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry and Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill.
authors.forename: Kimon
authors.initials: K
authors.lastname: Divaris
authors.affiliation: UNC Lineberger, School of Medicine, University of North Carolina at Chapel Hill.
authors.forename: William
authors.initials: W
authors.lastname: Seaman
authors.affiliation: UNC Lineberger, School of Medicine, University of North Carolina at Chapel Hill.|Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Webster-Cyriaque
authors.affiliation: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.|General Oral Health Clinic, School of Dentistry, University of North Carolina at Chapel Hill.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI.
authors.forename: Ning
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Catharine
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Prosthodontics, School of Dentistry, University of North Carolina at Chapel Hill.
authors.forename: Sompop
authors.initials: S
authors.lastname: Bencharit
authors.affiliation: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.|General Oral Health Clinic, School of Dentistry, University of North Carolina at Chapel Hill.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Teles
authors.affiliation: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.|General Oral Health Clinic, School of Dentistry, University of North Carolina at Chapel Hill.
authors.forename: Steven
authors.initials: S
authors.lastname: Offenbacher
mesh_terms: D000368:Aged; D016976:Aggregatibacter actinomycetemcomitans / Q000302:isolation & purification; D055113:Chronic Periodontitis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003773:Dental Plaque / Q000382:microbiology; D005260:Female; D016967:Fusobacterium nucleatum / Q000302:isolation & purification; D055106:Genome-Wide Association Study; D005881:Gingiva / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human
keywords: Genetics; immunity, innate; periodontitis; polymorphism, genetic