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

M. Munz, C. Willenborg, G.M. Richter, Y. Jockel-Schneider, C. Graetz, I. Staufenbiel, J. Wellmann, K. Berger, B. Krone, P. Hoffmann, N. van der Velde, A.G. Uitterlinden, L.C.P.G.M. de Groot, A.H. Sawalha, H. Direskeneli, G. Saruhan-Direskeneli, E. Guzeldemir-Akcakanat, H.G. Keceli, M. Laudes, B. NoackA. Teumer, B. Holtfreter, T. Kocher, P. Eickholz, J. Meyle, C. Doerfer, C. Bruckmann, W. Lieb, A. Franke, S. Schreiber, R.M. Nohutcu, J. Erdmann, B.G. Loos, S. Jepsen, H. Dommisch, A.S. Schaefer

Research output: Contribution to JournalArticleAcademicpeer-review


Periodontitis is one of the most 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 P = 1.09E-08 (rs4284742,-G; OR = 1.34, 95% CI = 1.21-1.48) and P = 5.48E-10 (rs2738058,-T; OR = 1.28, 95% CI = 1.18-1.38), respectively. SIGLEC5 is expressed in various myeloid immune cells and classified as an inhibitory receptor with the potential to mediate tyrosine phosphatases SHP-1/-2 dependent signaling. Alpha defensins are antimicrobial peptides with expression in neutrophils and mucosal 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
Issue number13
Publication statusPublished - Jul 2017

Bibliographical note

Correction published in: Human Molecular Genetics, Volume 27, Issue 5, 1 March 2018, Pages 941–942,.


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