A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Arne S Schaefer - , Kiel University (Author)
  • Arne Jochens - (Author)
  • Henrik Dommisch - (Author)
  • Christian Graetz - (Author)
  • Yvonne Jockel-Schneider - (Author)
  • Inga Harks - (Author)
  • Ingmar Staufenbiel - (Author)
  • Joerg Meyle - (Author)
  • Peter Eickholz - (Author)
  • Mathias Folwaczny - (Author)
  • Marja Laine - (Author)
  • Barbara Noack - , Department of Dental Maintenance, Periodontology (Author)
  • Cisca Wijmenga - (Author)
  • Wolfgang Lieb - (Author)
  • Corinna Bruckmann - (Author)
  • Stefan Schreiber - (Author)
  • Søren Jepsen - (Author)
  • Bruno G Loos - (Author)

Abstract

AIM: Epidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.

MATERIALS AND METHODS: Forty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls). Significant associations were replicated in 168 Dutch AgP cases and 679 controls and adjusted for the confounders smoking and sex.

RESULTS: Variants at IRF5 and PRDM1 showed association with AgP. Upon covariate adjustment for smoking and sex, the most strongly associated variant at IRF5 was the rare variant rs62481981 (ppooled = 0.0012, odds ratio [OR] = 3.1, 95% confidence interval [95% CI] = 1.6-6.1; 801 cases, 1476 controls).Within PRDM1 it was rs6923419 (ppooled = 0.004, OR = 0.7, 95% CI = 0.6-0.9; 833 cases, 1440 controls). The associations lost significance after correction for multiple testing in the replication. Both genes are implicated in beta-interferon signalling and are also genome-wide associated with SLE and inflammatory bowel disease.

CONCLUSION: The study gives no definite evidence for a pathogenic genetic link of periodontitis and RA but suggests IRF5 and PRDM1 as shared susceptibility factors.

Details

Original languageEnglish
Pages (from-to)1122-31
Number of pages10
JournalJournal of clinical periodontology
Volume41
Issue number12
Publication statusPublished - Dec 2014
Peer-reviewedYes

External IDs

ORCID /0000-0002-0423-7107/work/147142739
Scopus 84914687281

Keywords

Keywords

  • Aggressive Periodontitis/genetics, Arthritis, Rheumatoid/genetics, Case-Control Studies, Chromosome Mapping, Female, Genetic Predisposition to Disease/genetics, Genetic Variation/genetics, Genome-Wide Association Study, Genotype, Humans, Inflammatory Bowel Diseases/genetics, Interferon Regulatory Factors/genetics, Interferon-beta/genetics, Interleukin-2 Receptor alpha Subunit/genetics, Introns/genetics, Linkage Disequilibrium/genetics, Lupus Erythematosus, Systemic/genetics, Male, Positive Regulatory Domain I-Binding Factor 1, Repressor Proteins/genetics, Sex Factors, Signal Transduction/genetics, Smoking, Zinc Fingers/genetics