CHI3L1基因多态性和血清YKL-40水平与支气管哮喘发病的关联性

摘要

目的：观察几丁质酶3类1（CHI3L1）基因多态性与广东地区汉族人群哮喘发病的关联性，探讨采用其编码的几丁质酶样蛋白40（YKL-40）评估病情严重程度及监测病情的临床意义。方法：入选的251例研究对象分为哮喘组（150例）和正常对照组（101例）。采用 Massarray法检测 CHI3L1基因单核苷酸多态性（SNP），同时检测哮喘组和对照组研究对象血清 YKL-40水平、外周血嗜酸性粒细胞百分比（Eos％）、总 IgE和肺功能，同时将哮喘组分为急性加重期和稳定期2个亚组，比较患者血清 YKL-40水平的差异。结果：CHI3L1基因位点rs3806448 A/G等位基因在哮喘组和对照组中分布比较差异有统计学意义（P＜0.01），哮喘组患者 rs3806448等位基因 A频数明显高于正常对照组（OR＝1.93，95％CI＝1.30～2.62，χ2＝11.6，P＜0.01）；rs3806448基因型为AA患者血清YKL-40水平、总IgE和Eos％高于基因型为GG或AG患者（P＜0.05）；而rs3806448基因型为AA患者一秒用力呼气容积（FEV1）占预计值百分比（FEV1％）低于基因型为 GG或 AG患者（P＜0.05）；哮喘组患者血清YKL-40水平明显高于正常对照组（P＜0.01），哮喘急性加重组患者血清 YKL-40水平高于病情稳定组和正常对照组（P＜0.01）；哮喘组患者血清 YKL-40水平与外周血 EOS％及总 IgE 水平呈正相关关系（rEos＝0.348，rIgE＝0.437，P＜0.01），与肺功能呈负相关关系（r＝-0.745，P＜0.01）。结论：CHI3L1-rs3806448多态性与广东地区汉族人群的哮喘发病有关联，提示血清 YKL-40可能是评价哮喘患者病情严重程度及监测病情变化的一个新生物标志物。%Objective To investigate the association between CHI3L1 polymorphism and asthma in the Han population of Guangdong,and to explore the clinical values of chitinase-like protein YKL-40 in evaluating disease severity and monitoring the progression of the disease.Methods Total 251 objects were divided into asthma group (n=150)and control group(n=101).The single nucleotide polymorphism (SNP)at CHI3L1 gene was detected with Massarray method. The serum YKL-40 levels, total IgE levels, peripheral blood eosinophil percentage (Eos%)of the obj ects in asthma and control groups were detected. The asthma patients were divied into asthma exacergation group and stable group,and the serum YKL-40 levels were compared.Results The distribution of A/G at rs3806448 of CHI3L1 had significant difference between asthma and control groups (P<0.01 ), and the frequency of A allele at rs3806448 of the patients in asthma group was significantly higher than that in control group (OR= 1.93,95% CI=1.30-2.62,χ2=11.6,P<0.01).The serum YKL-40 levels,total IgE and Eos% of the patients with AA at rs3806448 were higher than those of the patients with GG or AG at rs3806448 (P<0.05);the FEV1% of the patients with AA was lower than those of the patients with GG or AG at rs3806448(P<0.01). The serum YKL-40 level of the patients in asthma group was significantly higher than that in normal control group (P<0.01),and the serum YKL-40 level of the patients in asthma exacergation group was higher than those in asthma stable group and normal control group(P<0.01).The serum YKL-40 level of the patients in asthma group was positively correlated with the peripheral blood Eos% and total IgE level(rEos=0.348,rIgE=0.437,P<0.01), and was negatively correlated with the lung function(r=-0.745,P<0.01). Conclusion The polymorphism of CHI3L1-rs3806448 may correlate with asthma of Han population in Guangdong area.The serum YKL-40 may be a new biomarker to evaluate asthma disease severity and helpful for monitoring illness stage.