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

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.

• Authors: Arne S Schaefer, Arne Jochens, Henrik Dommisch, Christian Graetz, Yvonne Jockel-Schneider, Inga Harks, Ingmar Staufenbiel, Joerg Meyle, Peter Eickholz, Mathias Folwaczny, Marja Laine, Barbara Noack, Cisca Wijmenga, Wolfgang Lieb, Corinna Bruckmann, Stefan Schreiber, Søren Jepsen, Bruno G Loos
• Journal: Journal of clinical periodontology (J Clin Periodontol) Vol. 41 Issue 12 Pg. 1122-31 (Dec 2014) ISSN: 1600-051X [Electronic] United States
• PMID: 25263394 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• 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

Topics

• 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)