A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis
| Autor: | Bastian Krone, Peter Eickholz, Birte Holtfreter, Klaus Berger, S. Jepsen, G. her Saruhan-Direskeneli, Henrik Dommisch, Christina Willenborg, Amr H. Sawalha, Corinna Bruckmann, Matthias Munz, Barbara Noack, Esra Guzeldemir-Akcakanat, Jeanette Erdmann, Ingmar Staufenbiel, Lisette C. P. G. M. de Groot, Yvonne Jockel-Schneider, Stefan Schreiber, Nathalie van der Velde, Arne S. Schaefer, Per Hoffmann, Wolfgang Lieb, Andre Franke, Thomas D. Kocher, Bruno G. Loos, Alexander Teumer, J. rgen Wellmann, Matthias Laudes, J. rg Meyle, Rahime M. Nohutcu, Christof Doerfer, Haner Direskeneli, Gesa M. Richter, Christian Graetz, Huseyin Gencay Keceli, André G. Uitterlinden |
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| Přispěvatelé: | Internal Medicine, Munz, Matthias, Willenborg, Christina, Richter, Gesa M., Jockel-Schneider, Yvonne, Graetz, Christian, Staufenbiel, Ingmar, Wellmann, Juergen, Berger, Klaus, Krone, Bastian, Hoffmann, Per, van der Velde, Nathalie, Uitterlinden, Andre G., de Groot, Lisette C. P. G. M., Sawalha, Amr H., Direskeneli, Haner, Saruhan-Direskeneli, Guher, Guzeldemir-Akcakanat, Esra, Keceli, Gencay, Laudes, Matthias, Noack, Barbara, Teumer, Alexander, Holtfreter, Birte, Kocher, Thomas, Eickholz, Peter, Meyle, Joerg, 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., Periodontology, Parodontologie (OII, ACTA), APH - Aging & Later Life, Geriatrics, AMS - Amsterdam Movement Sciences, Periodontoloji |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Turkey Turkish Statement (logic) Medizin RATIONALE Genome-wide association study 030204 cardiovascular system & hematology 0302 clinical medicine Risk Factors Lectins Aggressive periodontitis SUSCEPTIBILITY LOCUS Defensin Genetics (clinical) POPULATION Genetics Nucleotides General Medicine Middle Aged Phenotype Aggressive Periodontitis Chromosomal region language CORONARY-ARTERY-DISEASE Female Adult EXPRESSION medicine.medical_specialty alpha-Defensins Genotype Wish Antigens Differentiation Myelomonocytic Single-nucleotide polymorphism PHENOTYPES Sialic acid binding Biology Peptides Cyclic Polymorphism Single Nucleotide 03 medical and health sciences SDG 3 - Good Health and Well-being Antigens CD Molecular genetics RESOURCE REGRESSION medicine Life Science Humans Genetic Predisposition to Disease Molecular Biology VLAG Periodontitis Global Nutrition Wereldvoeding 030206 dentistry medicine.disease Chronic periodontitis language.human_language ALPHA-DEFENSIN 030104 developmental biology Research council Genetic Loci Case-Control Studies Immunology Chronic Periodontitis GENE COPY NUMBER Genome-Wide Association Study |
| Zdroj: | Human Molecular Genetics, 26(13), 2577-2588. Oxford University Press Human molecular genetics, 26(13), 2577-2588. Oxford University Press Human Molecular Genetics, 26(13), 2577-2588 Munz, M, Willenborg, C, Richter, G M, Jockel-Schneider, Y, Graetz, C, Staufenbiel, I, Wellmann, J, Berger, K, Krone, B, Hoffmann, P, van der Velde, N, Uitterlinden, A G, de Groot, L C P G M, Sawalha, A H, Direskeneli, H, Saruhan-Direskeneli, G, Guzeldemir-Akcakanat, E, Keceli, H G, Laudes, M, Noack, B, Teumer, A, Holtfreter, B, Kocher, T, Eickholz, P, Meyle, J, Doerfer, C, Bruckmann, C, Lieb, W, Franke, A, Schreiber, S, Nohutcu, R M, Erdmann, J, Loos, B G, Jepsen, S, Dommisch, H & Schaefer, A S 2017, ' A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis ', Human molecular genetics, vol. 26, no. 13, pp. 2577-2588 . https://doi.org/10.1093/hmg/ddx151 Human Molecular Genetics 26 (2017) 13 |
| ISSN: | 0964-6906 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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