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

doi:10.1038/s41467-018-05940-9

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

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.9(1), 3686

09/11/2018

DOI: 10.1038/s41467-018-05940-9

PMCID: PMC6134146

PMID: 30206230

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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 ) 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 ) associates with attenuated IL37 mRNA expression. Overall, we demonstrate that IL37 variants modulate the inflammatory cascade in periodontal disease.

Inflammation - pathology

Interleukin-1 - genetics

Leukocytes, Mononuclear - metabolism

Humans

Genetic Loci

Interleukin-1beta - genetics

RNA, Messenger - metabolism

Inflammation - blood

Stroke - genetics

Interleukin-1beta - blood

Genetic Variation

Tooth Loss - genetics

Haplotypes - genetics

Chronic Periodontitis - pathology

Inflammation - metabolism

Interleukin-1beta - metabolism

Chronic Periodontitis - genetics

HEK293 Cells

Periodontium - pathology

Female

Gingival Crevicular Fluid - metabolism

Disease Models, Animal

Amino Acid Sequence

Interleukin-1 - metabolism

Genome-Wide Association Study

RNA, Messenger - genetics

Mice, Transgenic

Animals

Polymorphism, Single Nucleotide - genetics

Chronic Periodontitis - blood

Details

Title: Subtitle: GWAS for Interleukin-1β levels in gingival crevicular fluid identifies IL37 variants in periodontal inflammation
Creators: Steven Offenbacher - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Yizu Jiao - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA. yizujiao@email.unc.edu
Steven J Kim - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Julie Marchesan - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Kevin L Moss - Department of Dental Ecology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Li Jing - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Kimon Divaris - Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
Sompop Bencharit - Department of General Practice, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA
Cary S Agler - Oral and Craniofacial Health Sciences, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Thiago Morelli - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Shaoping Zhang - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Lu Sun - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
William T Seaman - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
Dale Cowley - UNC Animal Models Core, University of North Carolina, Chapel Hill, NC, USA
Silvana P Barros - Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
James D Beck - Department of Dental Ecology, School of Dentistry, University of North Carolina, Chapel Hill, NC, USA
Matthias Munz - Institute for Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany
Arne S Schaefer - Department of Periodontology, Institute of Dental, Oral and Maxillary Medicine, Charité - University Medicine Berlin, Berlin, Germany
Kari E North - Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
Resource Type: Journal article
Publication Details: Nature communications, Vol.9(1), 3686
DOI: 10.1038/s41467-018-05940-9
PMID: 30206230
PMCID: PMC6134146
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: F32 DE026688 / U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR) T90DE02198 / U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR) R01DE023836 / U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)
Language: English
Date published: 09/11/2018
Academic Unit: Periodontics
Record Identifier: 9984065992302771

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