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


ABSTRACT: There is no agnostic GWAS evidence for the genetic control of IL-1? expression in periodontal disease. Here we report a GWAS for "high" gingival crevicular fluid IL-1? 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-1? in periodontal tissue. In RAW macrophages, PBMCs and transgenic mice, the IL37 variant increases expression of IL-1? 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.

SUBMITTER: Offenbacher S 

PROVIDER: S-EPMC6134146 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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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<sup>-22</sup>) 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  ...[more]

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