1. ¹Institute for Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Kiel, Germany
2. ²Institute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Kiel, Germany
3. ³Department of Oral Microbiology, Academic Center for Dentistry Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands
4. ⁴Department of Operative Dentistry and Periodontology, University Medical Center Schleswig-Holstein, Kiel, Germany
5. ⁵Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany
6. ⁶Zentrum für Zahn-, Mund- und Kieferheilkunde, Poliklinik für Zahnerhaltung, University Medical Center Carl Gustav Carus der Technischen Universität Dresden, Dresden, Germany
7. ⁷Department of Preventive Dentistry and Periodontology, University of Munich, Munich, Germany
8. ⁸Departement of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), VU University Amsterdam, Amsterdam, The Netherlands

Correspondence: Dr AS Schaefer, Institute for Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Schittenhelmstr. 12, Campus Kiel, House 6, Arnold-Heller-Str. 3, Kiel 24105, Germany. E-mail: a.schaefer@ikmb.uni-kiel.de

Received 12 February 2009; Revised 21 July 2009; Accepted 1 September 2009; Published online 15 October 2009.

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.