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Cited by 107Dermatology and Skin DiseasesAsthma and respiratory diseasesPsoriasis: Treatment and Pathogenesis

A functional IL-6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis

Esparza-Gordillo, Jorge, Schaarschmidt, Heidi, Liang, Liming, Cookson, William, Bauerfeind, Anja, Lee-Kirsch, Min-Ae, Nemat, Katja, Henderson, John +21 more·2013·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2013.01.057
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Abstract

Background Atopic dermatitis (AD) is a common inflammatory skin disease. Previous studies have revealed shared genetic determinants among different inflammatory disorders, suggesting that markers associated with immune-related traits might also play a role in AD. Objective We sought to identify novel genetic risk factors for AD. Methods We examined the results of all genome-wide association studies from a public repository and selected 318 genetic markers that were significantly associated with any inflammatory trait. These markers were considered candidates and tested for association with AD in a 3-step approach including 7 study populations with 7130 patients with AD and 9253 control subjects. Results A functional amino acid change in the IL-6 receptor (IL-6R Asp358Ala; rs2228145) was significantly associated with AD (odds ratio [OR], 1.15; P = 5 × 10(-9)). Interestingly, investigation of 2 independent population-based birth cohorts showed that IL-6R 358Ala specifically predisposes to the persistent form of AD (ORpersistent AD = 1.22, P = .0008; ORtransient AD = 1.04, P = .54). This variant determines the balance between the classical membrane-bound versus soluble IL-6R signaling pathways. Carriers of 358Ala had increased serum levels of soluble IL-6R (P = 4 × 10(-14)), with homozygote carriers showing a 2-fold increase. Moreover, we demonstrate that soluble IL-6R levels were higher in patients with AD than in control subjects (46.0 vs 37.8 ng/mL, P = .001). Additional AD r…

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  • IL-6R is associated with asthma and atopic dermatitis.

    “It was also reported that IL-6R is associated with asthma and atopic dermatitis (270, 271).”

    From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [271]

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Authors
Esparza-Gordillo, J., Schaarschmidt, H., Liang, L., Cookson, W., Bauerfeind, A., Lee-Kirsch, M.-A., Nemat, K., Henderson, J., Paternoster, L., Harper, J. I., Mangold, E., Nothen, M. M., Rüschendorf, F., Kerscher, T., Marenholz, I., Matanovic, A., Lau, S., Keil, T., Bauer, C.-P., Kurek, M., Ciechanowicz, A., Macek, M., Franke, A., Kabesch, M., Hubner, N., Abecasis, G., Weidinger, S., Moffatt, M., & Lee, Y.-A.
Affiliations
  • Max Delbrück Center (DE)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • Harvard University (US)
  • Imperial College London (GB)
  • Technische Universität Dresden (DE)
  • University of Bristol (GB)
  • Great Ormond Street Hospital (GB)
  • University of Bonn (DE)
  • Charité – Universitätsmedizin Berlin (DE)
  • Technical University of Munich (DE)
  • Pomeranian Medical University (PL)
  • University Hospital Regensburg (DE)
  • University of Michigan (US)
  • University Hospital Schleswig-Holstein (DE)
Corresponding author
Lee, Young-Ae
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2013-08
Volume
132
Issue
2
Pages
371-377
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2013.01.057
OpenAlex
W2064797995
Cited by
107
References
1
Citations by year
2026: 6 · 2025: 11 · 2024: 11 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 5 · 2017: 6 · 2016: 3 · 2015: 10 · 2014: 7 · 2013: 2
FWCI
8.57
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Bristol Research (University of Bristol) (publishedVersion)
  • University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion)
Funders
  • Wellcome Trust (097117, 092731)
  • Medical Research Council (MR/J012165/1)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
atopic dermatitis, IL-6 receptor, rs2228145, soluble IL-6 receptor, genetic risk factors, RAD50, RUNX3, HER3
MeSH terms
Adolescent, Alleles, Child, Child, Preschool, Dermatitis, Atopic, Female, Genotype, Humans, Infant, Infant, Newborn, Male, Risk Factors, Cohort Studies, Interleukin-6, Receptors, Interleukin-6, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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