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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Genetic and epigenetic regulation of YKL-40 in childhood
Journal of Allergy and Clinical Immunology, Volume 141, No. 3, Year 2018
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Description
Background: Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3–like 1 [CHI3L1]) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown. Objective: We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40 levels in the blood and (2) whether these biomarkers (CHI3L1 SNPs, methylation profiles, and YKL-40 levels) are associated with asthma in early childhood. Methods: We used data from up to 2405 participants from the Spanish Infancia y Medio Ambiente; the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey; and the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohorts. Associations between 68 CHI3L1 SNPs, methylation levels at 14 CHI3L1 CpG sites in whole-blood DNA, and circulating YKL-40 levels at 4 years of age were tested by using correlation analysis, multivariable regression, and mediation analysis. Each of these biomarkers was also tested for association with asthma at 4 years of age by using multivariable logistic regression. Results: YKL-40 levels were significantly associated with 7 SNPs and with methylation at 5 CpG sites. Consistent associations between these 7 SNPs (particularly rs10399931 and rs4950928) and 5 CpG sites were observed. Alleles linked to lower YKL-40 levels were associated with higher methylation levels. Participants with high YKL-40 levels (defined as the highest YKL-40 tertile) had increased odds for asthma compared with subjects with low YKL-40 levels (meta-analyzed adjusted odds ratio, 1.90 [95% CI, 1.08-3.36]). In contrast, neither SNPs nor methylation levels at CpG sites in CHI3L1 were associated with asthma. Conclusions: The effects of CHI3L1 genetic variation on circulating YKL-40 levels are partly mediated by methylation profiles. In our study YKL-40 levels, but not CHI3L1 SNPs or methylation levels, were associated with childhood asthma. © 2017 American Academy of Allergy, Asthma & Immunology
Authors & Co-Authors
Guerra, Stefano
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
United States, Tucson
The University of Arizona
Melén, Erik
Sweden, Stockholm
Karolinska Institutet
Sunyer, Jordi A.
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Spain, Barcelona
Institut Municipal D'investigacio Medica
Xu, Cheng Jian
Netherlands, Groningen
Rijksuniversiteit Groningen
Lavi, Iris
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Benet, Marta
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Bustamante, Mariona
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Spain, Barcelona
Centro de Regulacion Genomica, Barcelona
Dobaño, Carlota
Spain, Barcelona
Universitat de Barcelona
Guxens, M.
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Netherlands, Rotterdam
Erasmus Mc
Vrijheid, M.
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Kull, Inger
Sweden, Stockholm
Södersjukhuset
Sweden, Stockholm
Karolinska Institutet
Kumar, Ashish Madan
Sweden, Stockholm
Karolinska Institutet
Switzerland, Allschwil
Swiss Tropical and Public Health Institute Swiss Tph
Switzerland, Basel
Universitat Basel
Gehring, Ulrike
Netherlands, Utrecht
Universiteit Utrecht
Wickman, Magnus C.
Sweden, Stockholm
Karolinska Institutet
Bousquet, Jean J.
France, Villejuif
Centre de Recherche en Épidémiologie et Santé Des Populations
Postma, Dirkje S.
Netherlands, Groningen
Rijksuniversiteit Groningen
Antò, Josep María
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Spain, Barcelona
Institut Municipal D'investigacio Medica
Koppelman, Gerard H.
Netherlands, Groningen
Universitair Medisch Centrum Groningen
Statistics
Citations: 23
Authors: 18
Affiliations: 16
Identifiers
Doi:
10.1016/j.jaci.2017.06.030
ISSN:
00916749
Research Areas
Genetics And Genomics
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Study Approach
Quantitative