Zhang Ying, Wang Zhansheng, Ma Tongshuai
1 Department of Neonatal Intensive Care Unit, The First People's Hospital of Shangqiu , Shangqiu City, China .
2 Department of Pediatrics, The First People's Hospital of Shangqiu , Shangqiu City, China .
DNA Cell Biol. 2017 Aug;36(8):682-692. doi: 10.1089/dna.2017.3730. Epub 2017 Jun 7.
This study was aimed at investigating the correlation between genetic polymorphisms relevant to metabolic pathway of vitamin D3 (VD) and susceptibility to childhood bronchial asthma. Altogether 143 childhood patients with bronchial asthma and 143 healthy children of Chinese Han ethnicity were enrolled in this study. The key single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software and selected from previous investigations. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios and corresponding 95% confidence intervals were calculated to evaluate the association between SNPs and susceptibility to bronchial asthma. Statistical analyses were conducted by using SPSS 13.0 software. Rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR were shown to be significantly associated with increased risk of bronchial asthma. Besides, prognosis of childhood bronchial asthma, which was represented as Saint George Respiratory Questionnaire (SGRQ) scoring, was closely linked with CYP2R1 rs10766197, CYP27B1 rs4646536, VDR rs7975232, VDR rs1544410, PPAR rs1805192, and PPAR rs10865710. The haplotype analysis suggested that TA and CG of CG rs7041/rs4588, CA and AG of VDR rs7975232/rs1544410, and CC of PPAR rs1805192/rs10865710 were, respectively, correlated with levels of VD, IL-4, and IL-5. And only haplotypes of VDR showed associations with risk of bronchial asthma during childhood, whereas hardly any significance could be observed between the haplotypes and behavior of quality-of-life (SGRQ) scoring. Significant associations were found between rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR and susceptibility to and prognosis of childhood bronchial asthma, providing novel targets for treating the disorder.
本研究旨在探讨与维生素D3(VD)代谢途径相关的基因多态性与儿童支气管哮喘易感性之间的相关性。本研究共纳入143例中国汉族儿童支气管哮喘患者和143例健康儿童。关键单核苷酸多态性(SNP)通过HaploView 4.2软件进行鉴定,并从先前的研究中选取。使用TaqMan Blood DNA试剂盒从外周血样本中分离基因组DNA。通过TaqMan SNP基因分型检测进行SNP的基因分型。计算优势比及相应的95%置信区间,以评估SNP与支气管哮喘易感性之间的关联。使用SPSS 13.0软件进行统计分析。结果显示,CYP2R1的Rs10766197、CG的rs7041和rs4588、CYP27B1的rs4646536、VDR的rs2228570、rs7975232和rs1544410,以及PPAR的rs1805192和rs10865710与支气管哮喘风险增加显著相关。此外,以圣乔治呼吸问卷(SGRQ)评分表示的儿童支气管哮喘预后与CYP2R1 rs10766197、CYP27B1 rs4646536、VDR rs7975232、VDR rs1544410、PPAR rs1805192和PPAR rs10865710密切相关。单倍型分析表明,CG rs7041/rs4588的TA和CG、VDR rs7975232/rs1544410的CA和AG,以及PPAR rs1805192/rs10865710的CC分别与VD、IL-4和IL-5水平相关。并且只有VDR的单倍型与儿童期支气管哮喘风险相关,而单倍型与生活质量(SGRQ)评分行为之间几乎未观察到显著关联。发现CYP2R1的rs10766197、CG的rs7041和rs4588、CYP27B1的rs4646536、VDR的rs2228570、rs7975232和rs1544410,以及PPAR的rs1805192和rs10865710与儿童支气管哮喘易感性及预后显著相关,为该疾病的治疗提供了新的靶点。