Li Hongbin, Li Yuchun, Zhang Mingwu, Xu Guangchui, Feng Xianjun, Xi Jingzhuan, Zhao Bing
School of Public Health, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, P.R. China.
Biomed Rep. 2014 Jul;2(4):533-538. doi: 10.3892/br.2014.280. Epub 2014 May 19.
The aim of the present study was to explore the associations of genetic variants in the ADAM33 and TGF-β1 genes with the risk of childhood asthma. A total of 299 asthmatic children and 311 healthy controls were recruited in the hospital-based case-control study. The asthmatic subjects were further divided into mild and severe groups according to disease severity. Single-nucleotide polymorphisms (SNP) at ADAM33 V4, T2, S2 and T1, and TGF-β1 C-509T and T869C were selected and detected with PCR-RFLP. The associations of the SNPs with asthma risk and severity were analyzed. The associations between the haplotypes of ADAM33 and TGF-β1 were also evaluated. Compared with the GG genotype, the GC and CC genotypes at V4 were associated with an increased asthma risk in children and the ORs were 2.92 and 10.56, respectively. Compared with the CC genotype, the CT/TT genotype at C-509T was associated with an increased asthma risk and the OR was 2.26. Subsequent to stratification by asthma severity, compared with the V4 GG genotype, it was found that the CG and CC genotypes were associated with a mild asthma risk and the ORs were 3.00 and 5.99, respectively. The SNP at C-509T (CT/TT vs. CC) was associated with mild asthma (OR=2.34), whereas a marginally significant association was detected between the SNP (CT/TT vs. CC) and severe asthma risk (OR=2.19). The haplotype analysis revealed that, compared with the GGCA haplotype of ADAM33, significant associations of the haplotypes of CGCG, CGGA, GACA, GACG and GAGA with asthma risk were observed, and the ORs were 31.12, 12.24, 4.73, 30.85 and 4.83, respectively. No significant association was detected between the TGF-β1 haplotypes and asthma risk. The genetic variants at V4 and C-509T had the potential to modify the childhood asthma risk and the associations showed no notable difference with the disease severity. Thus, ADAM33 haplotypes provided more useful information in the prediction of asthma risk.
本研究的目的是探讨解聚素金属蛋白酶33（ADAM33）基因和转化生长因子-β1（TGF-β1）基因的遗传变异与儿童哮喘风险之间的关联。在这项基于医院的病例对照研究中，共招募了299名哮喘儿童和311名健康对照。根据疾病严重程度，哮喘受试者进一步分为轻度和重度组。选择ADAM33基因的V4、T2、S2和T1位点以及TGF-β1基因的C-509T和T869C位点的单核苷酸多态性（SNP），采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行检测。分析这些SNP与哮喘风险及严重程度之间的关联。同时也评估了ADAM33和TGF-β1基因单倍型之间的关联。与GG基因型相比，V4位点的GC和CC基因型与儿童哮喘风险增加相关，比值比（OR）分别为2.92和10.56。与CC基因型相比，C-509T位点的CT/TT基因型与哮喘风险增加相关，OR为2.26。按哮喘严重程度分层后，与V4位点的GG基因型相比，发现CG和CC基因型与轻度哮喘风险相关，OR分别为3.00和5.99。C-509T位点的SNP（CT/TT与CC相比）与轻度哮喘相关（OR=2.34），而该SNP（CT/TT与CC相比）与重度哮喘风险之间存在边缘显著关联（OR=2.19）。单倍型分析显示，与ADAM33基因的GGCA单倍型相比，观察到CGCG、CGGA、GACA、GACG和GAGA单倍型与哮喘风险显著相关，OR分别为31.12、12.24、4.73、30.85和4.83。未检测到TGF-β1基因单倍型与哮喘风险之间存在显著关联。V4位点和C-509T位点的遗传变异有可能改变儿童哮喘风险，且这些关联与疾病严重程度无显著差异。因此，ADAM33基因单倍型在预测哮喘风险方面提供了更有用的信息。
