Childhood asthma and spirometric indices are associated with polymorphic markers of two vitamin D 25-hydroxylase genes

Background: Polymorphic markers of vitamin D pathway genes have been associated with asthma traits in different White populations. This study investigated the relationship between asthma phenotypes and single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR), vitamin D binding protein (GC), two 25-hydroxylases (CYP2R1 and CYP27A1), and 1α-hydroxylase (CYP27B1) in Hong Kong Chinese children. Methods: 23 SNPs of the five vitamin D pathway genes were successfully genotyped in 914 asthmatic children and 1231 non-allergic controls. Genotypic and haplotypic associations with asthma phenotypes (diagnosis, spirometric indices, total IgE, and eosinophil percentage) were analyzed by multivariate regression. Generalized multifactor dimensionality reduction was used to detect epistatic interactions between SNPs for asthma phenotypes. Results: Several SNPs of CYP27A1, CYP27B1, GC, and CYP2R1 were associated with asthma or spirometric indices, although only the association between FEV₁ and CYP2R1 rs7935792 passed Bonferroni correction (p = 2.73 × 10^-4). Patients with CC genotype of rs7935792 had higher FEV₁ than those with the other two genotypes. Asthma was also associated with TT haplotype of CYP27A1 and AGGATA haplotype of CYP2R1 (p = 0.021 and 0.024, respectively). Besides, strong association was found between FEV₁ and GATAG of CYP2R1 (β = 13.37, p = 4.83 × 10^-4). GMDR failed to identify any 2-locus to 4-locus interaction that modulated asthma or spirometric indices. Conclusions: Several SNPs and haplotypes of CYP2R1 are associated with asthma diagnosis and FEV₁ in children. Asthma is also modestly associated with a CYP27A1 haplotype. These two 25-hydroxylase genes may be genetic determinants for asthma phenotypes in children.