Childhood asthma and spirometric indices are associated with polymorphic markers of two vitamin D 25‐hydroxylase genes
2015
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
vitaminD
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
haplotypicassociations with asthma phenotypes (diagnosis, spirometric indices, total IgE, and eosinophil percentage) were analyzed by multivariate regression. Generalized
multifactor dimensionality reductionwas 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
haplotypeof
CYP27A1and AGGATA
haplotypeof 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
haplotypesof 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.
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