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Background  YKL-40 is a chitinase-like glycoprotein encoded by the chitinase 3-like 1 gene,  CHI3L1 , localized at chromosome 1q32.1. Increased levels of serum YKL-40 have been reported to be a biomarker for asthma and a reduced lung function. Interestingly, the C-allele of the -131 C→G (rs4950928) polymorphism of  CHI3L1  has been shown to associate with bronchial hyperresponsiveness and reduced lung function suggesting that variations in  CHI3L1  may influence risk of asthma. The objective of the present study was to investigate the association of common variation in the  CHI3L1  locus with asthma, atopy and lung function in a large population-based sample of adults.    Methods/Principal Findings  Eleven single nucleotide polymorphisms (SNPs) of  CHI3L1  including rs4950928 were genotyped in 6514 individuals. Asthma was defined as self-reported history of physician-diagnosed asthma. Total IgE and specific IgE to inhalant allergens were measured on serum samples. Lung function was measured by spirometry. Homozygosity of the rs4950928 G allele as compared to homozygosity of the C allele was associated with self-reported physician diagnosed asthma (OR 1.5 (95% CI, 1.00–2.26)) and with prevalence of atopic asthma (OR 1.93 (95% CI, 1.21–3.07)) after adjustment for age, sex, smoking status, socio-economic class and BMI. Carriers of rs883125 G allele had a significantly lower prevalence of atopy (OR 0.82 (CI, 0.72; 0.94)) as compared to homozygosity of the C allele. None of the SNPs examined were significantly associated with FEV1. However, two SNPs (rs10399931and rs4950930) appeared to be significantly associated with FEV 1 /FVC-ratio. Subgroup analyses of never-smokers did not consistently influence the associations in an either positively og negatively way.    Conclusions  In contrast to previous studies, the rs4950928 G allele, and not the C allele, was found to be associated with asthma. A few other SNPs of the  CHI3L1  was found to be significantly associated with atopy and FEV1/FVC ratio, respectively. Thus, more studies seem warranted to establish the role of  CHI3L1  gene in asthma and atopy.

Association of Polymorphisms of the CHI3L1 Gene with Asthma and Atopy: A Populations-Based Study of 6514 Danish Adults