A Genome-wide Association Study of Periodontitis in a Japanese Population

Shimizu, Sayuri; Momozawa, Yukihide; Takahashi, Atsushi; Nagasawa, Toshiyuki; Ashikawa, Kyota; Terada, Yayoi; Izumi, Yuichi; Kobayashi, Hiroaki; Tsuji, Makoto; Kubo, Michiaki; Furuichi, Yasushi

doi:10.1177/0022034515570315

Cited by 63 publications

(62 citation statements)

References 34 publications

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“…Validity of the reported SNP associations will need to be further examined and replicated in a new study. However, it is important to note that identification of these genes was not based on traditional AAP/ADA classification for CP and AgP, which is used in other GWASs 10,44‐46 . Instead, these genes were first identified in the context of a PCT that used a combination of microorganisms and GCF–IL‐1β levels 14 .…”

Section: Discussionmentioning

confidence: 99%

Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease

Marchesan

Jiao

Moss

et al. 2017

Journal of Periodontology

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Background We investigated the single nucleotide polymorphism (SNP) context of a previously identified periodontitis-associated locus and examined its association with microbial, biological and periodontal disease clinical parameters. Methods We annotated a 200Kb-spanning region of 1q12 previously highlighted in a genome-wide association scan among 4,910 European American individuals (SNP rs1633266). Two haplotype blocks were selected. We examined the association of these polymorphisms with data on microbial plaque composition, gingival crevicular fluid (GCF)-interleukin (IL)-1β levels and clinical parameters of periodontal disease. Descriptive analysis of IFI16 and AIM2 protein expression in gingival tissues from healthy (n=2) and chronic periodontitis individuals (n=2) was done via immunohistochemistry. Results The highlighted locus is a 100Kb region containing the interferon gamma-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≥4mm (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 periodontal microorganisms and increased percentage of periodontal disease clinical parameters, suggesting the need for functional studies and additional fine-mapping of variants in the 1q12-locus.

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Section: Discussionmentioning

confidence: 99%

Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease

Marchesan

Jiao

Moss

et al. 2017

Journal of Periodontology

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“…Today, more than 1300 GWAS have been performed (www.ebi.ac.uk/gwas/), but only five GWAS have been performed in association with periodontitis; one in AgP and four in CP (49)(50)(51)(52)(53). Another GWAS in periodontitis studied SNPs in association with pathologic periodontal pocket depths, rather than in association with a certain form of periodontitis (54).…”

Section: The Genome-wide Association Study (Gwas) Approachmentioning

confidence: 99%

“…Only the GLT6D1 SNP rs1537415 remained significant in both AgP GWAS cohorts (Table 1) The most recent GWAS including a validation cohort was performed on 2760 Japanese CP cases and 15158 controls (53). No SNPs passed the high level of significance set for GWAS (p<5 x 10 -8 ), but two genetic loci were proposed for further replication and validation studies:…”

Section: Glt6d1 On Chromosomementioning

confidence: 99%

What is the Contribution of Genetics to Periodontal Risk?

Loos

Papantonopoulos

Jepsen

et al. 2015

Dental Clinics of North America

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This review addresses the multi-causal etiology of periodontitis, in which genetic factors play a role. The various proposed causes for periodontitis always play a role simultaneously, but the relative contribution of each of these, varies from case to case. In young individuals often with aggressive periodontitis (AgP) a stronger contribution from genetic factors is apparent, while in older individuals often with chronic periodontitis (CP), the relative contribution of the established subgingival biofilms (environmental factors) and life style factors (e.g. smoking, stress, diet), play a more dominant role in the phenotype of the disease.Nevertheless always some genetic susceptibility is present, for CP estimated at 25%.Periodontitis is therefore a complex disease, i.e. it behaves in a nonlinear fashion. Actually the disease progression rate fluctuates, where the disease sometimes moves into an aberrant state of host response and then swings back into a resolving state; in between, a settlement zone is present where essentially no differences are found for immunological parameters between cases with periodontitis and healthy controls. The genotype determines part of this fluctuation and the extent of it. The disease is polygenic, i.e. multiple genetic variants in multiple genes determine the phenotype, but there are individual and ethnic differences in the genes involved. We are still at the early stage to have identified the involved genes, in comparisons to other chronic diseases, we need to count on it that at least 100 causative genes across various global populations exist in AgP and CP. To date, the genetic variations firmly and repeatedly associated with periodontitis in some populations are found within the following genes: ANRIL, COX2, IL1, IL10, DEFB1, while many proposed periodontitis candidate genes have not been firmly proven or replicated. 3 KeypointsPeriodontitis is a multi-causal disease, with each of the causal factors playing a role but the relative contribution of these vary form case to case.The disease behaves in a nonlinear fashion, with periods of aberrant host response to periods within an active disease resolving state.To date only a few of the multitude of possible genetic factors for periodontitis are identified. Outline

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“…It should be noted, however, that these previous studies used different definitions of periodontal disease, study populations, and confounding factors, thus limiting the feasibility of inter-study comparisons. There are also several genome-wide association studies on periodontal disease (Teumer et al 2013;Shaffer et al 2014;Shimizu et al 2015), but none of these has reported an association for IL18 SNP. This is likely to be attributed to the low power of the studied sample sizes to reach genome-wide significance.…”

Section: Discussionmentioning

confidence: 99%

The<i> IL18</i> Promoter Polymorphism, rs1946518, Is Associated with the Risk of Periodontitis in Japanese Women: The Kyushu Okinawa Maternal and Child Health Study

Tanaka

Miyake

Hanioka

et al. 2017

Tohoku J. Exp. Med.

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Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in periodontitis and its polymorphisms might modulate the individual susceptibility to periodontitis. Only a limited number of studies on the association between IL18 single-nucleotide polymorphisms (SNPs) and the risk of periodontitis have been realized, however. The aim of this case-control study among young post-partum Japanese women (18 to 45 years) was to determine the impact of SNPs, rs1946518 (-607 C/A) and rs187238 (-137G/C), on periodontitis. The two SNPs may be located within a transcription factor-binding element, thereby influencing transcription from the IL18 promoter. Subjects were 131 cases who had at least one tooth with a probing pocket depth of ≥ 4.0 mm and 1,017 periodontally healthy controls. Probing pocket depth measurements were performed between 1 and 12 months post-partum. In this population, the A allele of rs1946518 and the C allele of rs187238 are more common. After adjustment for age, education, smoking, and use of an interdental brush, compared with subjects with the AA or AC genotype of SNP rs1946518, those with the CC genotype had a significantly reduced risk of periodontitis (adjusted odds ratio = 0.54, 95% confidence interval = 0.29-0.97). No significant association was observed between rs187238 and the risk of periodontitis. Our study did not reveal any evidence of interaction between the IL18 polymorphisms and smoking. Our findings indicate that the IL18 promoter SNP, rs1946518, is a potential risk factor of periodontitis among young Japanese women.

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A Genome-wide Association Study of Periodontitis in a Japanese Population

Cited by 63 publications

References 34 publications

Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease

Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease

What is the Contribution of Genetics to Periodontal Risk?

The<i> IL18</i> Promoter Polymorphism, rs1946518, Is Associated with the Risk of Periodontitis in Japanese Women: The Kyushu Okinawa Maternal and Child Health Study

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