Leung Ting Fan, Wang Susan Shuxin, Tang Man Fung, Kong Alice Pik-Shan, Sy Hing Yee, Hon Kam Lun, Chan Juliana Chung-ngor, Wong Gary Wing-kin
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Pediatr Allergy Immunol. 2015 Jun;26(4):375-82. doi: 10.1111/pai.12392.
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.
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.
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.
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.
维生素D通路基因的多态性标记已与不同白人人群的哮喘特征相关。本研究调查了香港华裔儿童哮喘表型与维生素D受体（VDR）、维生素D结合蛋白（GC）、两种25-羟化酶（CYP2R1和CYP27A1）以及1α-羟化酶（CYP27B1）的单核苷酸多态性（SNP）之间的关系。
在914名哮喘儿童和1231名非过敏对照中成功对五个维生素D通路基因的23个SNP进行了基因分型。通过多因素回归分析与哮喘表型（诊断、肺功能指标、总IgE和嗜酸性粒细胞百分比）的基因型和单倍型关联。使用广义多因素降维法检测SNP之间对哮喘表型的上位性相互作用。
CYP27A1、CYP27B1、GC和CYP2R1的几个SNP与哮喘或肺功能指标相关，尽管只有FEV1与CYP2R1 rs7935792之间的关联通过了Bonferroni校正（p = 2.73×10⁻⁴）。rs7935792的CC基因型患者的FEV1高于其他两种基因型的患者。哮喘还与CYP27A1的TT单倍型和CYP2R1的AGGATA单倍型相关（分别为p = 0.021和0.024）。此外，发现FEV1与CYP2R1的GATAG之间存在强关联（β = 13.37，p = 4.83×10⁻⁴）。GMDR未能识别出任何调节哮喘或肺功能指标的2位点至4位点相互作用。
CYP2R1的几个SNP和单倍型与儿童哮喘诊断和FEV1相关。哮喘也与CYP27A1单倍型有一定关联。这两个25-羟化酶基因可能是儿童哮喘表型的遗传决定因素。
