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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Offenbacher S,Jiao Y,Kim SJ,Marchesan J,Moss KL,Jing L,Divaris K,Bencharit S,Agler CS,Morelli T,Zhang S,Sun L,Seaman WT,Cowley D,Barros SP,Beck JD,Munz M,Schaefer AS,North KE

doi

10.1038/s41467-018-05940-9

subject

Has Abstract

pub_date

2018-09-11 00:00:00

pages

3686

issue

1

issn

2041-1723

pii

10.1038/s41467-018-05940-9

journal_volume

9

pub_type

杂志文章

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