{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:41:48Z","timestamp":1791416508489,"version":"4.3.3"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Rheumatology Research Foundation Disease Targeted Research Initiative"},{"name":"F. Gene and Rosemary Dixon Endowed Chair in Dentistry"},{"name":"Veterans Affairs Office of Research & Development"},{"name":"UNMC Clinical Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2016,4]]},"abstract":"Background and Objective<\/jats:title>Periodontitis results from interplay between genetic and environmental factors. Single nucleotide polymorphisms (SNP<\/jats:styled-content>s) in the coding region of the toll\u2010like receptor 4 gene (TLR<\/jats:styled-content>4<\/jats:italic>) may be associated with periodontitis, although previous studies have been inconclusive. Moreover, the interaction between environmental factors, such as cigarette smoking (a major risk factor for periodontitis), and Porphyromonas gingivalis<\/jats:italic> (a major periodontal pathogen) with the TLR<\/jats:styled-content>4<\/jats:italic> coding region Asp299Gly SNP<\/jats:styled-content> (rs4986790; a SNP<\/jats:styled-content> associated with lipopolysaccharide\u2010mediated inflammatory responses in periodontitis), have been largely ignored in previous reports. Therefore, the objective of this study was to examine the association between TLR<\/jats:styled-content>4<\/jats:italic> Asp299Gly (rs4986790) with alveolar bone height loss (ABHL<\/jats:styled-content>) and periodontitis, accounting for interactions between this SNP<\/jats:styled-content> with smoking and P.\u00a0gingivalis<\/jats:italic> prevalence. The CD<\/jats:styled-content>14<\/jats:italic>\/\u2010260 SNP (rs2569190) served as a control, as a recent meta\u2010analysis suggested no relationship between this SNP<\/jats:styled-content> and periodontitis.<\/jats:p><\/jats:sec>Material and Methods<\/jats:title>This multicenter study included 617 participants who had rheumatoid arthritis or osteoarthritis. This report presents a secondary outcome from the primary case\u2013control study examining the relationship of periodontitis with established rheumatoid arthritis. The Centers for Disease Control\/American Academy of Periodontology case definitions of periodontitis were used for this analysis. Participants received a full\u2010mouth clinical periodontal examination and panoramic radiograph. Percentage ABHL<\/jats:styled-content> was measured on posterior teeth. The TLR<\/jats:styled-content>4<\/jats:italic> Asp299Gly and CD<\/jats:styled-content>14<\/jats:italic>\/\u2010260 SNP<\/jats:styled-content>s were selected a priori and genotypes were determined using the ImmunoChip array (Illumina\u00ae<\/jats:sup>). Minor allele frequencies and associations with periodontitis and ABHL<\/jats:styled-content> did not differ according to rheumatoid arthritis vs. osteoarthritis status; therefore, data from these two groups were pooled. The presence of P.\u00a0gingivalis<\/jats:italic> was detected in subgingival plaque by PCR<\/jats:styled-content>. Multivariate ordinal logistic regression examined associations between the SNP<\/jats:styled-content>s and periodontitis or ABHL<\/jats:styled-content>. SNP<\/jats:styled-content> interactions with smoking and P.\u00a0gingivalis<\/jats:italic> were analyzed.<\/jats:p><\/jats:sec>Results<\/jats:title>A significant, negative interaction was observed between the TLR<\/jats:styled-content>4 <\/jats:italic>SNP<\/jats:styled-content> and the presence of P.\u00a0gingivalis<\/jats:italic> (p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.045) with respect to periodontitis. The TLR<\/jats:styled-content>4<\/jats:italic> minor variant was also associated with less ABHL<\/jats:styled-content>: 16.8% of individuals with low ABHL<\/jats:styled-content>, 9.0% with moderate ABHL<\/jats:styled-content> and 11.2% with high ABHL<\/jats:styled-content> had the minor allele [p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.029; odds ratio\u00a0=\u00a00.58 (95% confidence interval: 0.36\u20130.95)]. The interaction between the TLR<\/jats:styled-content>4 <\/jats:italic>SNP<\/jats:styled-content> and smoking was not significant with respect to periodontitis or ABHL<\/jats:styled-content>. The CD<\/jats:styled-content>14 <\/jats:italic>SNP<\/jats:styled-content> was not associated with periodontitis or ABHL<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The TLR<\/jats:styled-content>4<\/jats:italic> Asp299Gly SNP<\/jats:styled-content> significantly interacted with P.\u00a0gingivalis<\/jats:italic> in conferring a decreased risk of periodontitis and may be protective against ABHL<\/jats:styled-content>, a feature of periodontitis. Agents blocking TLR<\/jats:styled-content>4 signaling, a strategy currently under investigation for the treatment of other inflammatory conditions, may warrant investigation in the context of periodontitis related to the presence of P.\u00a0gingivalis<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12299","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T19:55:05Z","timestamp":1436903705000},"page":"203-211","source":"Crossref","is-referenced-by-count":29,"title":["TLR4<\/i> Asp299Gly polymorphism may be protective against chronic periodontitis"],"prefix":"10.1111","volume":"51","author":[{"given":"R. M.","family":"Sellers","sequence":"first","affiliation":[{"name":"University of Nebraska Medical Center College of Dentistry Lincoln NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. B.","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Surgical Specialties University of Nebraska Medical Center College of Dentistry Lincoln NE USA"},{"name":"Department of Internal Medicine College of Medicine University of Nebraska Medical Center Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Nebraska Medical Center College of Public Health Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. D.","family":"LeVan","sequence":"additional","affiliation":[{"name":"Omaha Veterans Affairs Medical Center and Department of Internal Medicine University of Nebraska Medical Center College of Medicine Omaha NE USA"},{"name":"Department of Epidemiology University of Nebraska Medical Center College of Public Health Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Oral Biology University of Florida College of Dentistry Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. R.","family":"Mikuls","sequence":"additional","affiliation":[{"name":"Omaha Veterans Affairs Medical Center and Department of Internal Medicine University of Nebraska Medical Center College of Medicine Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.080213"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1994.65.3.260"},{"key":"e_1_2_7_4_1","unstructured":"Office of the Surgeon General Office on Smoking and Health.Reports of the Surgeon General The Health Consequences of Smoking: A Report of the Surgeon General. 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