结核病患者服用抗结核药导致肝损害与GSTM1、GSTT1基因多态性关系的研究

发布时间：2018-07-06 15:21

  本文选题：抗结核药物 + 肝损害　； 参考：《河北北方学院》2013年硕士论文

【摘要】：基因多态性是药物性肝损害的一个重要的风险因素之一,抗结核药导致肝损害与基因多态性的研究是目前临床药理学研究的热点之一该项课题是对GSTM1和GSTT1无效基因型与结核病患者服用抗结核药导致肝损害的关系的研究,探讨这两个基因的无效基因型是否是导致肝损害的高风险因素。 收集解放军第309医院全军结核病研究所临床科室中服用异烟肼(INH)、利福平(RFP)、吡嗪酰胺(PZA)抗结核药的结核病患者血标本180例。根据年龄、性别、既往病史等条件进行综合打分,排除不符合的病例。最后筛选出124例患者纳入实验室实验阶段,其中肝损害患者(E组99例)。分成三组,分别包括：轻度肝损害者(B组46例)、中度肝损害者(C组23例)、重度肝损害者(D组30例)。对照组：非肝损害者(A组25例)。性别组成：男性64例、女性60例,年龄范围14-72岁。采血为外周血,放入EDTA管中,放置-4℃冰箱中，12h-36h内完成DNA提取,采用聚合酶链反应(PCR)进行DNA扩增。PCR的条件：GSTM1:94℃预变性5min；94℃变性60s,60℃退火60s,72℃延伸90s,循环35次；最后72℃延伸7min。GSTT1:94℃预变性4min；94℃变性45s,60℃退火45s,72℃延伸45s,循环35次；最后72℃延伸7min。分析GSTM1及GSTT1无效基因型分布频率 通过T-test分析：B、C、D、E组的GSTM1基因分布频率存在显著性差异(P0.01); B、D、E组.的GSTT1的基因分布频率存在显著性差异(P0.01)；C组GSTT1基因分布频率无显著性差异(P0.05),本实验经偏札相关分析：GSTM1(r=0.204,P0.01)、GSTT1(r=0.204,P0.01)无效基因型分布频率与非肝损害之间无显著相关性；GSTM1(r=0.588, P0.01)、GSTT1(r=0.558, P0.01)无效基因分布频率与轻度肝损害之间有显著相关性；GSTM1(r=0.693, P0.01)、GSTT1(r=0.625,P0.01)无效基因分布频率与中度肝损害之间有显著相关性；GSTM1(r=0.590, P0.01)、GSTT1(r=0.550,P0.01),无效基因分布频率与重度肝损害之间有显著相关性；GSTM1(r=0.835, P0.01)、GSTT1(r=0.845, P0.01)无效基因分布频率与肝损害(轻、中、重)之间有显著相关性。 GSTM1、GSTT1无效基因型分别与服用抗结核药导致肝损害有明显统计学差异,即：GSTM1、GSTT1基因多态性与抗结核药导致肝损害呈正相关。
[Abstract]:Gene polymorphism is one of the important risk factors for drug-induced liver damage. The study of liver damage and gene polymorphism induced by antituberculotics is one of the hot topics in clinical pharmacology. The study is concerned with the relationship between the invalid genotypes of GSTM1 and GSTT1 and liver damage induced by anti-tuberculosis drugs in patients with tuberculosis. To investigate whether the invalid genotypes of these two genes are high risk factors for liver damage. The blood samples of 180 tuberculosis patients taking isoniazid (INH), rifampicin (RFP) and pyrazinamide (PZA) were collected. According to the age, gender, past medical history and other conditions for comprehensive scoring, excluding the case. 124 patients were selected to be included in the laboratory experiment, including 99 patients with liver injury (group E). They were divided into three groups: mild liver injury (group B, 46 cases), moderate liver injury (group C, 23 cases) and severe liver damage (group D, 30 cases). Control group: non-hepatic injury (group A, 25 cases). Sex composition: 64 males and 60 females aged 14-72 years. Blood was collected from peripheral blood and placed in EDTA tube. DNA extraction was completed within 12h-36 h in refrigerator at -4 鈩，

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