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中国临床药理学与治疗学 ›› 2021, Vol. 26 ›› Issue (11): 1250-1258.doi: 10.12092/j.issn.1009-2501.2021.11.005

• 临床药理学 • 上一篇    下一篇

吸入性糖皮质激素布地奈德相关基因多态性与哮喘疗效的关系

李静,马丽娟,袁圆,王捷,郁长治,赵军   

  1. 新疆医科大学第一附属医院药学部,乌鲁木齐  830011,新疆维吾尔自治区
  • 收稿日期:2021-06-26 修回日期:2021-08-10 出版日期:2021-11-26 发布日期:2021-12-03
  • 通讯作者: 赵军,女,硕士,主任药师,副教授,研究方向:治疗药物监测与临床药学方向。 Tel: 0991-4365513 E-mail: zhaojun700326@163.com
  • 作者简介:李静,女,硕士,主管药师,研究方向:个体化用药基因检测与临床药理学的相关研究。 Tel: 0991-4365513 E-mail: 1275998459@qq.com
  • 基金资助:
    省部共建中亚高发病成因与防治国家重点实验室精准医学研究专项(SKL-HIDCA-2020-JZ3) 

Relationship between gene polymorphism of inhaled glucocorticosteroids budesonide and efficacy in asthma

LI Jing, Ma Lijuan, YUAN Yuan, WANG Jie, YU Changzhi, ZHAO Jun   

  1. Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi  830011, Xinjiang Uygur Autonomous Region, China
  • Received:2021-06-26 Revised:2021-08-10 Online:2021-11-26 Published:2021-12-03

摘要: 目的:研究糖皮质激素诱导转录因子1(GLCCI1)基因rs37973、促肾上腺皮质激素释放激素受体1(CRHR1)基因rs1876828以及IgE低亲和力II受体基因Fc片段(FCER2)基因rs28364072基因多态性与哮喘患者使用吸入性糖皮质激素(ICS)布地奈德治疗疗效的关系。方法:收集哮喘患者血样152例,提取血液DNA,采用荧光原位杂交法检测GLCCI1、CRHR1与FCER2基因多态性,收集患者进行药物治疗前后的肺功能检测结果,记录用力肺活量(FVC)、第一秒用力呼气容积(FEV1)、第一秒用力呼气容积占用力肺活量的百分比(FEV1/FVC%)、嗜酸性粒细胞计数(EOS)等指标,并计算FVC、FEV1、FEV1/FVC等差值和改善率。分析GLCCI1、CRHR1与FCER2基因多态性与哮喘患者治疗前后肺功能改变的关系。结果:GLCCI1、FCER2各基因型的分布频率在汉族患者与维族患者中均有统计学差异(P<0.05),本研究人群中未发现CRHR1 AA基因型,但GA基因型在维族患者中的分布频率明显高于汉族患者(P<0.05)。GLCCI1 AA型与GG型患者治疗前后的FVC差值与FVC改善率变化相近(P>0.05),但AG型患者的FVC差值与FVC改善率较之GG型明显升高(P<0.05);FCER2 AA型与AG型相比,药物治疗前后FEV1/FVC的差值变化相近(P>0.05),但AA型/AG型分别与GG型相比,ICS治疗前后FEV1/FVC的差值均明显升高(P<0.05)。CRHR1 GA基因型患者治疗前后的FEV1/FVC差值比GG型的变化更明显(P<0.05)。FCER2 AA型与GG型的汉族与维族患者经治疗后的各项肺功能指标变化均相近(P>0.05),而AG基因型的维族患者与汉族患者相比,经ICS治疗后的FEV1改善率、FEV1/FVC差值和FEV1/FVC改善率均有明显升高(P<0.05)。结论:GLCCI1、CRHR1、FCER2各基因型患者经吸入性糖皮质激素布地奈德治疗前后肺功能指标的改变具有明显差异,GLCCI1 rs37973、CRHR1 rs1876828与FCER2 rs28364072基因多态性与哮喘患者ICS治疗疗效存在一定相关性,可能作为预测哮喘患者吸入性糖皮质激素治疗疗效的遗传学指标。

关键词: 吸入性糖皮质激素布地奈德, 药物基因多态性, 支气管哮喘, 疗效

Abstract: AIM: To investigate the relationship among the rs37973 polymorphism of glucocorticoid induced transcription factor 1 (GLCCI1) gene, the rs1876828 polymorphism of corticotropin-hormone receptor 1 (CRHR1) gene, the rs28364072 polymorphism of Fc fragment of IgE receptor II (FCER2) gene and the response to inhaled corticosteroids (ICS) budesonide in patients with asthma.  METHODS: 152 blood samples of patients with asthma were collected. The DNA were studied by blood samples. Fluorescence in situ hybridization method was used to detect the polymorphism of GLCCI1,  CRHR1, FCER2. Lung function index of the ICS before and after treatment, such as forced vital capacity (FVC), first second forced breath volume (FEV1) and first second forced breath volume of forced lung (FEV1/FVC%), and Eosinophil count (EOS) et al. were collected. The change value of FVC, FEV1, FEV1/FVC and their improvement rate were calculated. The relationship between GLCCI1, CRHR1 and FCER2 gene polymorphism and altered lung function before and after treatment in asthma patients was analyzed. RESULTS: There was significant difference between Han and Uyghur asthmatic patients in the distribution frequency of GLCCI1 and FCER2 genotypes. No CRHR1 AA genotype was found in the study population, but there was significant difference between Han and Uyghur patients in the distribution frequency of CRHR1 GG and GA genotype. The difference of FVC and the improvement rate of FVC in GLCCI1 AA type and GG type patients was similar before and after treatment (P>0.05), but the difference of FVC and the improvement rate of FVC in AG type patients were significantly increased compared with GG type patients' (P<0.05). The difference of FEV1/FVC before and after drug treatment in FCER2 AA and AG genotype was similar (P>0.05), but the difference of FEV1/FVC before and after ICS treatment in FCER2 AA and AG genotype was significantly higher than that in GG (P<0.05). The difference of FEV1/FVC before and after treatment in patients with CRHR1 GA genotype was more significant than that with GG genotype (P<0.05). Han and Uygur patients with FCER2 AA and GG genotype had similar changes in pulmonary function indexes after treatment (P>0.05), while Uygur patients with AG genotype had significantly increased in FEV1 improvement rate, FEV1/FVC difference and FEV1/FVC improvement rate after ICS treatment compared with Han patients (P<0.05).CONCLUSION: There was relevance among GLCCI1 rs37973, CRHR1 rs1876828, FCER2 rs28364072 gene polymorphism and lung function in inhaled corticoids budesonide treatment, which may be a genetic indicator to predict the efficacy of inhaled glucocorticoids in asthma patients.

Key words: inhaled glucocorticoids budesonide, gene polymorphism, bronchial asthma, efficacy

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