Abstract
BackgroundSingle nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1), the gene encoding YKL-40, and increased serum YKL-40 levels are associated with severe forms of asthma. It has never been addressed whether SNPs in CHI3L1 and cord blood YKL-40 levels could already serve as potential biomarkers for milder forms of asthma. We assessed in an unselected population whether SNPs in CHI3L1 and cord blood YKL-40 levels at birth are associated with respiratory symptoms, lung function changes, asthma, and atopy.MethodsIn a prospective birth cohort of healthy term-born neonates (n = 260), we studied CHI3L1 polymorphisms, and measured cord blood YKL-40 levels by ELISA in (n = 170) infants. Lung function was performed at 5 weeks and 6 years. Respiratory health during the first year of life was assessed weekly by telephone interviews. Diagnosis of asthma and allergic sensitisation was assessed at 6 years (n = 142).ResultsThe SNP rs10399805 was significantly associated with asthma at 6 years. The odds ratio for asthma was 4.5 (95 % CI 1.59–12.94) per T-allele. This finding was unchanged when adjusting for cord blood YKL-40 levels. There was no significant association for cord blood YKL-40 levels and asthma. SNPs in CHI3L1 and cord blood YKL-40 were not associated with lung function measurements at 5 weeks and 6 years, respiratory symptoms in the first year, and allergic sensitisation at 6 years.ConclusionGenetic variation in CHI3L1 might be related to the development of milder forms of asthma. Larger studies are warranted to establish the role of YKL-40 in that pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0239-8) contains supplementary material, which is available to authorized users.
Highlights
Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1), the gene encoding YKL-40, and increased serum YKL-40 levels are associated with severe forms of asthma
Usemann et al BMC Pulmonary Medicine (2016) 16:81 of single nucleotide polymorphisms (SNPs) in CHI3L1 and cord blood YKL-40 with asthma at school age was found [6]. It remains unknown if genetic variations in CHI3L1 or cord blood YKL-40 levels assessed at birth in unselected infants are associated with milder forms of childhood asthma
We studied in a birth cohort of unselected infants the association of SNPs in CHI3L1 and cord blood YKL-40 levels with asthma development
Summary
Methods are detailed in Additional file 1. In order to capture the elevated cord blood YKL-40 levels with the limited range of the ELISA, samples had to be pre-diluted 1:20 before measurement. YKL-40 was categorised in quintiles and associations of YKL-40 levels were calculated using the Cochran-Armitage trend test, shown as Ptrend. Lung function was performed according to ERS/ATS standards [13]. Outcomes at 6 years Respiratory health was assessed using questions from the International Study of Asthma and Allergies in Childhood [14]. Risk factors Exposure to pre- and postnatal risk factors [11, 14, 17] on outcomes are given in Additional file 1: Table S1. Maternal asthma (self-reported or doctor-diagnosed), maternal atopic disease (history of allergic rhinitis, allergic asthma or atopic dermatitis), and parental education were assessed. Associations were calculated: (a) unadjusted and, (b) adjusted for known and potential
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