Projects per year
Abstract
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 language | English |
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Article number | 3686 |
Journal | Nature Communications |
Volume | 9 |
Issue number | 1 |
ISSN | 1751-8628 |
DOIs | |
Publication status | Published - 01.12.2018 |
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
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Dive into the research topics of 'GWAS for Interleukin-1β levels in gingival crevicular fluid identifies IL37 variants in periodontal inflammation'. Together they form a unique fingerprint.Projects
- 1 Finished
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Genome-wide Association Study for the Identification of Genetic Risk Factors of Periodontitis
Schäfer, A. (Principal Investigator (PI)), Erdmann, J. (Associated Staff), Franke, A. (Associated Staff), Jepsen, S. (Associated Staff), Krawczak, M. (Associated Staff), Loos, B. G. (Associated Staff) & Padyukov, L. (Associated Staff)
01.01.14 → 31.12.18
Project: DFG Projects › DFG Individual Projects