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

• Published in: Genes and immunity Vol. 11; no. 1; pp. 45 - 54
• Main Authors: Schaefer, A S, Richter, G M, Nothnagel, M, Laine, M L, Rühling, A, Schäfer, C, Cordes, N, Noack, B, Folwaczny, M, Glas, J, Dörfer, C, Dommisch, H, Groessner-Schreiber, B, Jepsen, S, Loos, B G, Schreiber, S
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2010
• Subjects: 3' Untranslated regions; 3' Untranslated Regions - genetics; Adult; Aggressive Periodontitis - genetics; Aggressive Periodontitis - metabolism; Aggressive Periodontitis - pathology; Antimicrobial agents; Bacteria; beta-Defensins - genetics; beta-Defensins - metabolism; Binding sites; Cardiovascular disease; Chronic Periodontitis - genetics; Chronic Periodontitis - metabolism; Chronic Periodontitis - pathology; Confidence intervals; Connective tissue; Defensins; Dentistry; Diabetes; Female; Gender; Gene polymorphism; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Gum disease; Haplotypes; Health risk assessment; Humans; Immune system; Inflammatory diseases; Male; MicroRNAs; Middle Aged; miRNA; Molecular biology; Pathogens; Periodontal diseases; Periodontics; Periodontitis; Periodontium; Physiological aspects; Polymorphism, Single Nucleotide; Promoters; Regression analysis; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Germany; Netherlands
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2009.75

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.