GWAS for Interleukin-1β levels in gingival crevicular fluid identifies IL37 variants in periodontal inflammation

Steven Offenbacher, Yizu Jiao*, Steven J. Kim, Julie Marchesan, Kevin L. Moss, Li Jing, Kimon Divaris, Sompop Bencharit, Cary S. Agler, Thiago Morelli, Shaoping Zhang, Lu Sun, William T. Seaman, Dale Cowley, Silvana P. Barros, James D. Beck, Matthias Munz, Arne S. Schaefer, Kari E. North

*Corresponding author for this work
2 Citations (Scopus)


There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal disease. Here we report a GWAS for “high” gingival crevicular fluid IL-1β expression among 4910 European-American adults and identify association signals in the IL37 locus. rs3811046 at this locus (p = 3.3 × 10−22) is associated with severe chronic periodontitis (OR = 1.50; 95% CI = 1.12–2.00), 10-year incident tooth loss (≥3 teeth: RR = 1.33; 95% CI = 1.09–1.62) and aggressive periodontitis (OR = 1.12; 95% CI = 1.01–1.26) in an independent sample of 4927 German/Dutch adults. The minor allele at rs3811046 is associated with increased expression of IL-1β in periodontal tissue. In RAW macrophages, PBMCs and transgenic mice, the IL37 variant increases expression of IL-1β and IL-6, inducing more severe periodontal disease, while IL-37 protein production is impaired and shows reduced cleavage by caspase-1. A second variant in the IL37 locus (rs2708943, p = 4.2 × 10−7) associates with attenuated IL37 mRNA expression. Overall, we demonstrate that IL37 variants modulate the inflammatory cascade in periodontal disease.

Original languageEnglish
Article number3686
JournalNature Communications
Issue number1
Publication statusPublished - 01.12.2018

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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