IADR Abstract Archives
IFI16 and AIM2 variants are associated with periodontal disease
Objectives: The purpose of this study was to investigate the genomic and single nucleotide polymorphism (SNP) context of a previously identified periodontitis-associated locus on chromosome 1q12 and examine its association with periodontal microorganisms, gingival-crevicular fluid (GCF) IL-1β levels and clinical measures of periodontal disease.
Methods: We annotated a 200Kb-spanning region of 1q12 that was previously highlighted in a genome-wide association scan of periodontal complex traits among 4,910 European American subjects (lead SNP—rs1633266; minor allele frequency=0.12; p=3.1x10-8). We scanned for additional variants with suggestive evidence of association (p<5x10-6) and potential functional roles in adjacent genes. We used LocusZoom and SNPNexus for locus visualization and prediction of SNP functional implications. We examined the association of these polymorphisms among subsets of European American subjects with data on microbial plaque composition (n=909), (GCF) IL-1β levels (n=4,407) and periodontal parameters (n=4,766) including probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP). We used generalized linear models to test these associations using a conventional p<0.05 statistical significance threshold.
Results: The highlighted locus is a 100Kb region containing the interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes. Twenty-two SNPs in two tight linkage disequilibrium blocks demonstrated suggestive evidence of association (p<5x10-6). Three SNPs intronic to IFI16 (rs6940, rs1057027, rs1057028) are coding non-synonymous. Functional predictions suggest that rs6940 and rs1057028 are potentially/probably damaging to the IFI16 protein structure. Rs2793845, rs6940 and rs1057028 were significantly associated with increased levels of several periodontal microorganisms even after adjusting for plaque scores and extent BOP. Rs6940 and rs1057028 were significantly associated with increased GCF IL-1β levels and mean and extent PD.
Conclusions: This study found IFI16 and AIM2 SNPs associated with higher levels periodontal microorganisms and more severe periodontal disease, suggesting the need for functional studies and additional fine-mapping of variants in the 1q12 locus.
Methods: We annotated a 200Kb-spanning region of 1q12 that was previously highlighted in a genome-wide association scan of periodontal complex traits among 4,910 European American subjects (lead SNP—rs1633266; minor allele frequency=0.12; p=3.1x10-8). We scanned for additional variants with suggestive evidence of association (p<5x10-6) and potential functional roles in adjacent genes. We used LocusZoom and SNPNexus for locus visualization and prediction of SNP functional implications. We examined the association of these polymorphisms among subsets of European American subjects with data on microbial plaque composition (n=909), (GCF) IL-1β levels (n=4,407) and periodontal parameters (n=4,766) including probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP). We used generalized linear models to test these associations using a conventional p<0.05 statistical significance threshold.
Results: The highlighted locus is a 100Kb region containing the interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes. Twenty-two SNPs in two tight linkage disequilibrium blocks demonstrated suggestive evidence of association (p<5x10-6). Three SNPs intronic to IFI16 (rs6940, rs1057027, rs1057028) are coding non-synonymous. Functional predictions suggest that rs6940 and rs1057028 are potentially/probably damaging to the IFI16 protein structure. Rs2793845, rs6940 and rs1057028 were significantly associated with increased levels of several periodontal microorganisms even after adjusting for plaque scores and extent BOP. Rs6940 and rs1057028 were significantly associated with increased GCF IL-1β levels and mean and extent PD.
Conclusions: This study found IFI16 and AIM2 SNPs associated with higher levels periodontal microorganisms and more severe periodontal disease, suggesting the need for functional studies and additional fine-mapping of variants in the 1q12 locus.