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

J Clin Periodontol. 2014 Dec;41(12):1122-31. doi: 10.1111/jcpe.12314. Epub 2014 Nov 15.

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.

Keywords: IRF5; PRDM1; inflammatory bowel disease; periodontitis; rheumatoid arthritis; systemic lupus erythrematosus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • IL2RA protein, human
  • IRF5 protein, human
  • Interferon Regulatory Factors
  • Interleukin-2 Receptor alpha Subunit
  • Repressor Proteins
  • PRDM1 protein, human
  • Interferon-beta
  • Positive Regulatory Domain I-Binding Factor 1