CHI3L1基因单核苷酸多态性与儿童哮喘易感性的相关性研究

Association between CHI3L1 SNPs and susceptibility to childhood asthma

摘要:

目的 探讨CHI3L1基因单核苷酸多态性(SNP)与儿童哮喘易感性之间的相关性.方法 选取2011年1月至2013年10月确诊为哮喘的316例儿童为哮喘组,同期选取297例健康儿童作为对照组.采集所有研究对象外周血,应用化学发光法和流式细胞术分别检测两组总IgE水平和嗜酸性粒细胞比例,ELISA法检测YKL-40水平;提取外周血细胞基因组DNA,应用Mass ARRAY-IPLEX质谱阵列技术检测CHI3L1基因rs4950928、rs10399805和rs883125位点的单核苷酸多态性,统计分析上述位点基因型及等位基因分布频率.结果 哮喘组总IgE和YKL-40浓度均较对照组显著升高(均P<0.05),而嗜酸性粒细胞比例在两组间差异无统计学意义(P>0.05).哮喘组rs883125位点的GG基因型频率高于对照组(P<0.05).rs4950928位点CC基因型在哮喘组中的频率低于对照组,而CG基因型频率则高于对照组(P<0.05);该位点GG和CG基因型的哮喘组患儿总IgE和YKL-40水平相对CC基因型患儿明显升高(P<0.05).结论 YKL-40可作为初步诊断儿童哮喘的分子标记物;CHI3L1基因的rs4950928和rs883125多态性可能为儿童哮喘的易感因子;rs4950928位点G等位基因可能是提高哮喘风险的易感因子.

Abstract:

Objective To investigate the association between CHI3L1 single nucleotide polymorphisms (SNPs) and the susceptibility to childhood asthma. Methods A total of 316 children diagnosed with asthma between January 2011 and October 2013 and 297 healthy children were selected as asthma group and control group respectively. Peripheral blood samples were collected from all subjects. Chemiluminescence and flow cytometry were applied to measure total IgE level and the percentage of eosinophils. ELISA was used to measure YKL-40 level. Genomic DNA was extracted from peripheral blood hemocytes, and the genotype and allele frequencies at CHI3L1 SNPs rs4950928, rs10399805, and rs883125 were determined by MALDI-TOP mass spectrometry. Results The total IgE and YKL-40 levels were significantly higher in the asthma group than in the control group (P<0.05), while the percentage of eosinophils showed no significant difference between the two groups (P>0.05). The frequency of GG genotype at rs883125 in the asthma group was significantly higher than that in the control group (P<0.05). For rs4950928, the asthma group had a significantly lower frequency of CC genotype (P<0.05) but a significantly higher frequency of CG genotype (P<0.05) compared with the control group. In the asthma group, the patients with GG and CG genotypes at rs4950928 had significantly increased total IgE and YKL-40 levels compared with those with CC genotype at this locus (P<0.05). Conclusions YKL-40 is a potential molecular biomarker for the primary diagnosis of childhood asthma. CHI3L1 SNPs rs4950928 and rs883125 may be associated with childhood asthma. G allele at rs4950928 may increase the risk of childhood asthma.