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 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.
Schaefer
A S
AS
Institute for Clinical Molecular Biology, University Medical Center Schleswig-Holstein, Kiel, Germany. a.schaefer@ikmb.uni-kiel.de
Richter
G M
GM
Nothnagel
M
M
Laine
M L
ML
Rühling
A
A
Schäfer
C
C
Cordes
N
N
Noack
B
B
Folwaczny
M
M
Glas
J
J
Dörfer
C
C
Dommisch
H
H
Groessner-Schreiber
B
B
Jepsen
S
S
Loos
B G
BG
Schreiber
S
S
D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D010520:Aggressive Periodontitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055113:Chronic Periodontitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C406407:DEFB1 protein, human; D023083:beta-Defensins