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A 3′ UTR transition within DEFB1 is associated with chronic and aggressive periodontitis

Genes & Immunity volume 11, pages 45–54 (2010)Cite this article

Abstract

Periodontal diseases are complex inflammatory diseases and affect up to 20% of the worldwide population. An unbalanced reaction of the immune system toward microbial pathogens is considered as the key factor in the development of periodontitis. Defensins have a strong antimicrobial function and are important contributors of the immune system toward maintaining health. Here, we present the first systematic association study of DEFB1. Using a haplotype-tagging single nucleotide polymorphism (SNP) approach, including described promoter SNPs of DEFB1, we investigated the associations of the selected variants in a large population (N=1337 cases and 2887 ethnically matched controls). The 3′ untranslated region SNP, rs1047031, showed the most significant association signal for homozygous carriers of the rare A allele (P=0.002) with an increased genetic risk of 1.3 (95% confidence interval: 1.11–1.57). The association was consistent with the specific periodontitis forms: chronic periodontitis (odds ratio=2.2 (95% confidence interval: 1.16–4.35), P=0.02), and aggressive periodontitis (odds ratio=1.3 (95% confidence interval 1.04–1.68), P=0.02). Sequencing of regulatory and exonic regions of DEFB1 identified no other associated variant, pointing toward rs1047031 as likely being the causative variant. Prediction of microRNA targets identified a potential microRNA-binding site at the position of rs1047031.

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Acknowledgements

The following dentists are gratefully acknowledged. They have helped with the recruitment of patients and are listed alphabetically: PGGL van der Avoort, G Althoff, DS Barendregt, MS Bertels, A Biggel, R Bodens, F Bröseler, C Christan, NHC Corba, F Cleve, BM Deblauwe, LJ van Dijk, RA Driessen, T Eger, A Engelmann, U Engelsmann, A Friedmann, P Eickholz, PA Eigenhuis, J Graswinckel, LJMM Gründemann, H Hamming, L Hanfland, W Heindl, B Heinz, JW Hutter, J Jansen, H Jentsch, G Knöfler, A Krug, WH van Leeuwen, Ch. Lienhard, A Manschot, F Meier, E Meijer, O Oberbeckmann, MDA Petit, AM van Puijenbroek, V Reichert, B Sigusch, B Simon, A Spahr, JA Speelman, NB Spits, J Stein, J Steinfort, RWR Steures, C Theben, C Tietmann, H Topoll, JAH Tromp, ATE Vangsted, Varoufaki, GA Voerman, K Wagner, GA van der Weijden and E van der Zee. This study was supported by a research grant of the ‘Research Center Inflammation Medicine’ of the Medical Faculty, Christian-Albrechts-University, University Medical Center Schleswig-Holstein, Campus Kiel (ASS and GMR); by the German Ministry of Education and Research (BMBF) through a National Genome Research Network (NGFN 01GS0809) grant (MN); by a grant from the Deutsche Forschungsgemeinschaft (KFO208) (ASS, GMR, HD and SJ); by the German Ministry of Education and Research through the popgen biobank project (01GR0468); by a grant from BONFOR of the Medical Faculty, University of Bonn (SJ) and a grant from the ARPA Research Foundation (BG-S and SJ), Regensburg, Germany.

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Authors and Affiliations

  1. Institute for Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Kiel, Germany

    A S Schaefer, G M Richter & S Schreiber

  2. Institute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Kiel, Germany

    M Nothnagel

  3. Department of Oral Microbiology, Academic Center for Dentistry Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands

    M L Laine

  4. Department of Operative Dentistry and Periodontology, University Medical Center Schleswig-Holstein, Kiel, Germany

    A Rühling, N Cordes, C Dörfer & B Groessner-Schreiber

  5. Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany

    C Schäfer, H Dommisch & S Jepsen

  6. Zentrum für Zahn-, Mund- und Kieferheilkunde, Poliklinik für Zahnerhaltung, University Medical Center Carl Gustav Carus der Technischen Universität Dresden, Dresden, Germany

    B Noack

  7. Department of Preventive Dentistry and Periodontology, University of Munich, Munich, Germany

    M Folwaczny & J Glas

  8. Departement of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), VU University Amsterdam, Amsterdam, The Netherlands

    B G Loos

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  1. A S Schaefer
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Correspondence to A S Schaefer.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Schaefer, A., Richter, G., Nothnagel, M. et al. A 3′ UTR transition within DEFB1 is associated with chronic and aggressive periodontitis. Genes Immun 11, 45–54 (2010). https://doi.org/10.1038/gene.2009.75

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