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Hum Mol Genet. 2017 Jul 1;26(13):2577-2588. doi: 10.1093/hmg/ddx151.

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

Author information

1
Department of Periodontology and Synoptic Dentistry, Institute of Dental, Oral and Maxillary Medicine, Charité - University Medicine Berlin, Germany.
2
Institute for Integrative and Experimental Genomics, University Medical Center Schleswig-Holstein - Campus Lübeck, Germany.
3
Department of Periodontology, Clinic of Preventive Dentistry and Periodontology, University Medical Center of the Julius-Maximilians-University, Würzburg, Germany.
4
Department of Operative Dentistry and Periodontology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
5
Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Hannover, Germany.
6
Institute of Epidemiology and Social Medicine, University Münster, Germany.
7
Institute of Medical Informatics, Biometry and Epidemiology, University Clinic Essen, Germany.
8
Institute of Human Genetics, University of Bonn, Germany.
9
Human Genomics Research Group, Department of Biomedicine, University Hospital of Basel, Switzerland.
10
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
11
Department of Internal Medicine Section of Geriatrics, Amsterdam Medical Center, Amsterdam, The Netherlands.
12
Department of Epidemiology and the EMGO Institute of Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
13
Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
14
Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, USA.
15
Division of Rheumatology, Marmara University, School of Medicine, Istanbul, Turkey.
16
Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
17
Department of Periodontology, Faculty of Dentistry, Kocaeli University, Turkey.
18
Department of Periodontology, Faculty of Dentistry, Hacettepe University, Sihhiye, Ankara, Turkey.
19
Clinic of Internal Medicine, University Clinic Schleswig-Holstein, Kiel, Germany.
20
Clinic of Conservational Dentistry, Center of Dental, Oral and Maxillary Medicine, University Medical Center Carl-Gustav-Carus, Technical University Dresden, Germany.
21
Institute for Community Medicine, University Medicine Greifswald, Germany.
22
Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pedodontics, Dental School, University Medicine Greifswald, Germany.
23
Department of Periodontology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
24
Department of Periodontology, University Medical Center Giessen and Marburg, Germany.
25
Department of Conservative Dentistry and Periodontology, Medical University Vienna, School of Dentistry, Vienna, Austria.
26
Institute of Epidemiology, Biobank PopGen, Christian-Albrechts-University, Kiel, Germany.
27
Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
28
Department of Periodontology and Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, The Netherlands.
29
Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany.

Abstract

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.

PMID:
28449029
DOI:
10.1093/hmg/ddx151
[Indexed for MEDLINE]

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