Genetic and epigenetic regulation of YKL-40 in childhood

Autor: Iris Lavi, Stefano Guerra, Martine Vrijheid, Pieter van der Vlies, Cheng-Jian Xu, Ulrike Gehring, Ashok Kumar, Marta Benet, Erik Melén, Mariona Bustamante, Jordi Sunyer, Josep M. Antó, Anne-Elie Carsin, Magnus Wickman, Jean Bousquet, Carlota Dobaño, Mònica Guxens, Dorieke J. Dijkstra, Christina Tischer, Inger Kull, Cilla Söderhäll, Dirkje S. Postma, Gerard H. Koppelman, Anna Bergström
Přispěvatelé: One Health Chemisch, dIRAS RA-2, Child and Adolescent Psychiatry / Psychology, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Groningen Research Institute for Asthma and COPD (GRIAC)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Journal of Allergy and Clinical Immunology, 141(3), 1105-1114. Mosby Inc.
Journal of Allergy and Clinical Immunology
Journal of Allergy and Clinical Immunology, Elsevier, 2018, 141 (3), pp.1105-1114. ⟨10.1016/j.jaci.2017.06.030⟩
Journal of Allergy and Clinical Immunology, 141(3), 1105. Mosby Inc.
Journal of Allergy and Clinical Immunology, 141(3), 1105-1114. MOSBY-ELSEVIER
ISSN: 0091-6749
Popis: 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.
Databáze: OpenAIRE
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