A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis

Matthias Munz, Christina Willenborg, Gesa M. Richter, Yvonne Jockel-Schneider, Christian Graetz, Ingmar Staufenbiel, Jürgen Wellmann, Klaus Berger, Bastian Krone, Per Hoffmann, Nathalie Van Der Velde, André G. Uitterlinden, Lisette de Groot, Amr H. Sawalha, Haner Direskeneli, Güher Saruhan-Direskeneli, Esra Guzeldemir-Akcakanat, Gencay Keceli, Matthias Laudes, Barbara NoackAlexander Teumer, Birte Holtfreter, Thomas Kocher, Peter Eickholz, Jörg Meyle, Christof Doerfer, Corinna Bruckmann, Wolfgang Lieb, Andre Franke, Stefan Schreiber, Rahime M. Nohutcu, Jeanette Erdmann, Bruno G. Loos, Soeren Jepsen, Henrik Dommisch, Arne S. Schaefer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)

Abstract

Periodontitis is one of themost common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an
estimated heritability of 50%. The disease is characterized by destruction of the alveolar bone due to an aberrant host
inflammatory response to a dysbiotic oral microbiome. Previous genome-wide association studies (GWAS) have reported several
suggestive susceptibility loci. Here, we conducted a GWAS using a German and Dutch case-control sample of aggressive periodontitis
(AgP, 896 cases, 7,104 controls), a rare but highly severe and early-onset form of periodontitis, validated the associations in a
German sample of severe forms of the more moderate phenotype chronic periodontitis (CP) (993 cases, 1,419 controls). Positive
findings were replicated in a Turkish sample of AgP (223 cases, 564 controls). A locus at SIGLEC5 (sialic acid binding Ig-like lectin 5)
and a chromosomal region downstream of the DEFA1A3 locus (defensin alpha 1-3) showed association with both disease phenotypes
and were associated with periodontitis at a genome-wide significance level in the pooled samples, with P¼1.09E-08
(rs4284742,-G; OR¼1.34, 95% CI¼1.21–1.48) and P¼5.48E-10 (rs2738058,-T; OR¼1.28, 95% CI¼1.18–1.38), respectively. SIGLEC5 is
expressed in various myeloid immune cells and classified as an inhibitory receptor with the potential tomediate tyrosine phosphatases
SHP-1/-2 dependent signaling. Alpha defensins are antimicrobial peptides with expression in neutrophils andmucosal
surfaces and a role in phagocyte-mediated host defense. This study identifies the first shared genetic risk loci of AgP and CP
with genome-wide significance and highlights the role of innate and adaptive immunity in the etiology of periodontitis.
Original languageEnglish
Pages (from-to)2577-2588
JournalHuman Molecular Genetics
Volume26
Issue number13
DOIs
Publication statusPublished - 2017

Fingerprint Dive into the research topics of 'A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis'. Together they form a unique fingerprint.

Cite this