Imperial College London
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ProfessorMarjo-RiittaJarvelin

Faculty of Medicine, School of Public Health

Chair in Lifecourse Epidemiology
 
 
 
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+44 (0)20 7594 3345m.jarvelin

 
 
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Location

 

156Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Guerra:2018:10.1016/j.jaci.2017.06.030,
author = {Guerra, S and Melén, E and Sunyer, J and Xu, CJ and Lavi, I and Benet, M and Bustamante, M and Carsin, AE and Dobaño, C and Guxens, M and Tischer, C and Vrijheid, M and Kull, I and Bergström, A and Kumar, A and Söderhäll, C and Gehring, U and Dijkstra, DJ and van, der Vlies P and Wickman, M and Bousquet, J and Postma, DS and Anto, JM and Koppelman, GH},
doi = {10.1016/j.jaci.2017.06.030},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1105--1114},
title = {Genetic and epigenetic regulation of YKL-40 in childhood},
url = {http://dx.doi.org/10.1016/j.jaci.2017.06.030},
volume = {141},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - © 2017 American Academy of Allergy, Asthma  &  Immunology 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 cir
AU  - Guerra,S
AU  - Melén,E
AU  - Sunyer,J
AU  - Xu,CJ
AU  - Lavi,I
AU  - Benet,M
AU  - Bustamante,M
AU  - Carsin,AE
AU  - Dobaño,C
AU  - Guxens,M
AU  - Tischer,C
AU  - Vrijheid,M
AU  - Kull,I
AU  - Bergström,A
AU  - Kumar,A
AU  - Söderhäll,C
AU  - Gehring,U
AU  - Dijkstra,DJ
AU  - van,der Vlies P
AU  - Wickman,M
AU  - Bousquet,J
AU  - Postma,DS
AU  - Anto,JM
AU  - Koppelman,GH
DO  - 10.1016/j.jaci.2017.06.030
EP  - 1114
PY  - 2018///
SN  - 0091-6749
SP  - 1105
TI  - Genetic and epigenetic regulation of YKL-40 in childhood
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2017.06.030
VL  - 141
ER  -
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