J Periodontol. 2017 Jul;88(7):663-672. doi: 10.1902/jop.2017.160553. Epub 2017 Apr 07.
Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease.
Journal of periodontology
Julie T Marchesan, Yizu Jiao, Kevin Moss, Kimon Divaris, William Seaman, Jennifer Webster-Cyriaque, Shaoping Zhang, Ning Yu, Catharine Song, Sompop Bencharit, Ricardo Teles, Steven Offenbacher
- 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.
- Department of Pediatric Dentistry, School of Dentistry and Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill.
- 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.
- Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI.
- Department of Prosthodontics, School of Dentistry, University of North Carolina at Chapel Hill.
PMCID: PMC5695043 DOI: 10.1902/jop.2017.160553
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.
Keywords: Genetics; immunity, innate; periodontitis; polymorphism, genetic
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