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Childhood asthma and spirometric indices are associated with polymorphic markers of two vitamin D 25‐hydroxylase genes
Author(s) -
Leung Ting Fan,
Wang Susan Shuxin,
Tang Man Fung,
Kong Alice Pikshan,
Sy Hing Yee,
Hon Kam Lun,
Chan Juliana Chungngor,
Wong Gary Wingkin
Publication year - 2015
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12392
Subject(s) - multifactor dimensionality reduction , asthma , medicine , single nucleotide polymorphism , snp , haplotype , genotype , vitamin d binding protein , vitamin d and neurology , genetics , biology , gene
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 ( SNP s) of vitamin D receptor ( VDR ), vitamin D binding protein ( GC ), two 25‐hydroxylases ( CYP 2R1 and CYP 27A1 ), and 1α‐hydroxylase ( CYP 27B1 ) in Hong Kong Chinese children. Methods 23 SNP s 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 SNP s for asthma phenotypes. Results Several SNP s of CYP 27A1 , CYP 27B1 , GC , and CYP 2R1 were associated with asthma or spirometric indices, although only the association between FEV 1 and CYP 2R1 rs7935792 passed Bonferroni correction (p = 2.73 × 10 −4 ). Patients with CC genotype of rs7935792 had higher FEV 1 than those with the other two genotypes. Asthma was also associated with TT haplotype of CYP 27A1 and AGGATA haplotype of CYP 2R1 (p = 0.021 and 0.024, respectively). Besides, strong association was found between FEV 1 and GATAG of CYP 2R1 (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 SNP s and haplotypes of CYP 2R1 are associated with asthma diagnosis and FEV 1 in children. Asthma is also modestly associated with a CYP 27A1 haplotype. These two 25‐hydroxylase genes may be genetic determinants for asthma phenotypes in children.