PMID- 26174031
OWN - NLM
STAT- MEDLINE
DCOM- 20180509
LR  - 20181202
IS  - 1600-0765 (Electronic)
IS  - 0022-3484 (Linking)
VI  - 51
IP  - 2
DP  - 2016 Apr
TI  - TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis.
PG  - 203-11
LID - 10.1111/jre.12299 [doi]
AB  - BACKGROUND AND OBJECTIVE: Periodontitis results from interplay between genetic 
      and environmental factors. Single nucleotide polymorphisms (SNPs) in the coding 
      region of the toll-like receptor 4 gene (TLR4) 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 (a major periodontal 
      pathogen) with the TLR4 coding region Asp299Gly SNP (rs4986790; a SNP associated 
      with lipopolysaccharide-mediated inflammatory responses in periodontitis), have 
      been largely ignored in previous reports. Therefore, the objective of this study 
      was to examine the association between TLR4 Asp299Gly (rs4986790) with alveolar 
      bone height loss (ABHL) and periodontitis, accounting for interactions between 
      this SNP with smoking and P. gingivalis prevalence. The CD14/-260 SNP (rs2569190) 
      served as a control, as a recent meta-analysis suggested no relationship between 
      this SNP and periodontitis. MATERIAL AND METHODS: This multicenter study included 
      617 participants who had rheumatoid arthritis or osteoarthritis. This report 
      presents a secondary outcome from the primary case-control 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-mouth 
      clinical periodontal examination and panoramic radiograph. Percentage ABHL was 
      measured on posterior teeth. The TLR4 Asp299Gly and CD14/-260 SNPs were selected 
      a priori and genotypes were determined using the ImmunoChip array (Illumina((R)) ). 
      Minor allele frequencies and associations with periodontitis and ABHL did not 
      differ according to rheumatoid arthritis vs. osteoarthritis status; therefore, 
      data from these two groups were pooled. The presence of P. gingivalis was 
      detected in subgingival plaque by PCR. Multivariate ordinal logistic regression 
      examined associations between the SNPs and periodontitis or ABHL. SNP 
      interactions with smoking and P. gingivalis were analyzed. RESULTS: A 
      significant, negative interaction was observed between the TLR4 SNP and the 
      presence of P. gingivalis (p = 0.045) with respect to periodontitis. The TLR4 
      minor variant was also associated with less ABHL: 16.8% of individuals with low 
      ABHL, 9.0% with moderate ABHL and 11.2% with high ABHL had the minor allele 
      [p = 0.029; odds ratio = 0.58 (95% confidence interval: 0.36-0.95)]. The 
      interaction between the TLR4 SNP and smoking was not significant with respect to 
      periodontitis or ABHL. The CD14 SNP was not associated with periodontitis or 
      ABHL. CONCLUSION: The TLR4 Asp299Gly SNP significantly interacted with 
      P. gingivalis in conferring a decreased risk of periodontitis and may be 
      protective against ABHL, a feature of periodontitis. Agents blocking TLR4 
      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. gingivalis.
CI  - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Sellers, R M
AU  - Sellers RM
AD  - University of Nebraska Medical Center College of Dentistry, Lincoln, NE, USA.
FAU - Payne, J B
AU  - Payne JB
AD  - Department of Surgical Specialties, University of Nebraska Medical Center College 
      of Dentistry, Lincoln, NE, USA.
AD  - Department of Internal Medicine, College of Medicine, University of Nebraska 
      Medical Center, Omaha, NE, USA.
FAU - Yu, F
AU  - Yu F
AD  - Department of Biostatistics, University of Nebraska Medical Center College of 
      Public Health, Omaha, NE, USA.
FAU - LeVan, T D
AU  - LeVan TD
AD  - Omaha Veterans Affairs Medical Center and Department of Internal Medicine, 
      University of Nebraska Medical Center College of Medicine, Omaha, NE, USA.
AD  - Department of Epidemiology, University of Nebraska Medical Center College of 
      Public Health, Omaha, NE, USA.
FAU - Walker, C
AU  - Walker C
AD  - Department of Oral Biology, University of Florida College of Dentistry, 
      Gainesville, FL, USA.
FAU - Mikuls, T R
AU  - Mikuls TR
AD  - Omaha Veterans Affairs Medical Center and Department of Internal Medicine, 
      University of Nebraska Medical Center College of Medicine, Omaha, NE, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150714
PL  - United States
TA  - J Periodontal Res
JT  - Journal of periodontal research
JID - 0055107
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Case-Control Studies
MH  - Chronic Periodontitis/*genetics
MH  - Humans
MH  - Periodontitis
MH  - *Polymorphism, Single Nucleotide
MH  - Porphyromonas gingivalis
MH  - Toll-Like Receptor 4/*genetics
OTO - NOTNLM
OT  - Porphyromonas gingivalis
OT  - alveolar bone loss
OT  - cluster of differentiation (CD) antigens
OT  - periodontitis
OT  - single nucleotide polymorphism
OT  - toll-like receptors
EDAT- 2015/07/16 06:00
MHDA- 2018/05/10 06:00
CRDT- 2015/07/16 06:00
PHST- 2015/05/12 00:00 [accepted]
PHST- 2015/07/16 06:00 [entrez]
PHST- 2015/07/16 06:00 [pubmed]
PHST- 2018/05/10 06:00 [medline]
AID - 10.1111/jre.12299 [doi]
PST - ppublish
SO  - J Periodontal Res. 2016 Apr;51(2):203-11. doi: 10.1111/jre.12299. Epub 2015 Jul 
      14.