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

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 30 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. Genes and Immunity (2010) 11, 45-54; doi:10.1038/gene.2009.75; published online 15 October 2009