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

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....

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Veröffentlicht in:Human molecular genetics Jg. 26; H. 13; S. 2577
Hauptverfasser: Munz, Matthias, Willenborg, Christina, Richter, Gesa M, Jockel-Schneider, Yvonne, Graetz, Christian, Staufenbiel, Ingmar, Wellmann, Jürgen, Berger, Klaus, Krone, Bastian, Hoffmann, Per, van der Velde, Nathalie, Uitterlinden, André G, de Groot, Lisette C P G M, Sawalha, Amr H, Direskeneli, Haner, Saruhan-Direskeneli, Güher, Guzeldemir-Akcakanat, Esra, Keceli, Huseyin Gencay, Laudes, Matthias, Noack, Barbara, Teumer, Alexander, Holtfreter, Birte, Kocher, Thomas, Eickholz, Peter, Meyle, Jörg, Doerfer, Christof, Bruckmann, Corinna, Lieb, Wolfgang, Franke, Andre, Schreiber, Stefan, Nohutcu, Rahime M, Erdmann, Jeanette, Loos, Bruno G, Jepsen, Soeren, Dommisch, Henrik, Schaefer, Arne S
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.07.2017
Schlagworte:
Adult
Aggressive Periodontitis - genetics
alpha-Defensins - genetics
alpha-Defensins - metabolism
Antigens, CD - genetics
Antigens, CD - metabolism
Antigens, Differentiation, Myelomonocytic - genetics
Antigens, Differentiation, Myelomonocytic - metabolism
Case-Control Studies
Chronic Periodontitis - genetics
Female
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Lectins - genetics
Lectins - metabolism
Male
Middle Aged
Nucleotides
Peptides, Cyclic - genetics
Peptides, Cyclic - metabolism
Phenotype
Polymorphism, Single Nucleotide - genetics
Risk Factors
Turkey
ISSN:1460-2083, 1460-2083
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1460-2083
1460-2083
DOI:10.1093/hmg/ddx151