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

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 (p(pooled) = 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 (p(pooled) = 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.