title: Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia.
abstract: BACKGROUND
  Patients with severe congenital neutropenia (SCN) often develop periodontitis despite standard medical and dental care. In light of previous findings that mutations in the neutrophil elastase gene, ELANE, are associated with more severe neutropenic phenotypes, we hypothesized an association between the genotype of SCN and development of periodontitis.
  
  
  METHODS
  Fourteen Swedish patients with SCN or cyclic neutropenia harboring different genetic backgrounds were recruited for periodontal examination. Peripheral blood, gingival crevicular fluid (GCF), and subgingival bacterial samples were collected. The levels of cytokines and antibacterial peptides were determined in GCF and plasma by multiplex immunoassay and immunoblotting, respectively. Subgingival bacterial samples were analyzed using 16S rDNA pyrosequencing.
  
  
  RESULTS
  ELANE mutations correlated with more severe periodontal status than the HAX1 or unknown mutations in patients with SCN. The subjects with mutant ELANE had higher levels of IL-1β in GCF. Using principal coordinate analysis of the subgingival microbiota, patients with ELANE mutations and reference subjects with periodontitis tended to cluster differently from patients with HAX1 or unknown mutations and non-periodontitis reference subjects.
  
  
  CONCLUSIONS
  This study demonstrates an association between ELANE mutations in SCN and the development of periodontitis with skewed subgingival microbiota, indicating a potential role of ELANE mutations in the pathogenesis of periodontitis.
authors.affiliation: Division of Pediatric Dentistry, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.forename: Göran
authors.initials: G
authors.lastname: Carlsson
authors.forename: Biniyam
authors.initials: B
authors.lastname: Wondimu
authors.forename: Annika
authors.initials: A
authors.lastname: Fahlén
authors.forename: Jenny
authors.initials: J
authors.lastname: Karlsson-Sjöberg
authors.forename: Mats
authors.initials: M
authors.lastname: Andersson
authors.forename: Lars
authors.initials: L
authors.lastname: Engstrand
authors.forename: Tülay
authors.initials: T
authors.lastname: Yucel-Lindberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Modéer
authors.forename: Katrin
authors.initials: K
authors.lastname: Pütsep
mesh_terms: D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002648:Child; D000080984:Congenital Bone Marrow Failure Syndromes; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005881:Gingiva / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009503:Neutropenia / Q000151:congenital* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D010518:Periodontitis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D011110:Polymorphism, Genetic; D013548:Sweden; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D004269:DNA, Bacterial; D019272:Leukocyte Elastase; D054804:Cathelicidins