title: A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Arne S
authors.initials: AS
authors.lastname: Schaefer
authors.forename: Arne
authors.initials: A
authors.lastname: Jochens
authors.forename: Henrik
authors.initials: H
authors.lastname: Dommisch
authors.forename: Christian
authors.initials: C
authors.lastname: Graetz
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Jockel-Schneider
authors.forename: Inga
authors.initials: I
authors.lastname: Harks
authors.forename: Ingmar
authors.initials: I
authors.lastname: Staufenbiel
authors.forename: Joerg
authors.initials: J
authors.lastname: Meyle
authors.forename: Peter
authors.initials: P
authors.lastname: Eickholz
authors.forename: Mathias
authors.initials: M
authors.lastname: Folwaczny
authors.forename: Marja
authors.initials: M
authors.lastname: Laine
authors.forename: Barbara
authors.initials: B
authors.lastname: Noack
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Corinna
authors.initials: C
authors.lastname: Bruckmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Loos
mesh_terms: D010520:Aggressive Periodontitis / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008297:Male; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics*; D012737:Sex Factors; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: C508017:IL2RA protein, human; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D016899:Interferon-beta; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: IRF5; PRDM1; inflammatory bowel disease; periodontitis; rheumatoid arthritis; systemic lupus erythrematosus