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

Authors:
A S Schaefer, G M Richter, M Nothnagel, M L Laine, A Rühling, C Schäfer, N Cordes, B Noack, M Folwaczny, J Glas, C Dörfer, H Dommisch, B Groessner-Schreiber, S Jepsen, B G Loos, S Schreiber
Year of publication:
2010
Volume:
11
Issue:
1
Issn:
1466-4879
Journal title abbreviated:
GENES IMMUN
Journal title long:
Genes and immunity
Impact factor:
2.472
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.