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目的探讨细胞色素P450 1A2和2C19基因多态性与抗结核药物性肝损伤的相关性。方法采用1∶1病例对照研究,以抗结核药治疗致肝损伤的结核病患者为病例组,无肝损伤者为对照组,共179对。采用聚合酶链反应限制性片段长度多态方法检测CYP1A2基因734C/A和CYP2C19基因681G/A位点基因型。采用SPSS17.0条件Logistic回归进行数据分析。结果CYP1A2基因734C/A位点C、A等位基因频率在病例组和对照组频率分别为37.2%、62.8%、和47.2%、52.8%;CYP2C19基因的681G/A位点G、A等位基因频率在病例组和对照组频率分别为59.8%、40.2%和62.8%、37.2%,CYP1A2基因734C/A位点多态性与抗结核药物性肝损伤的发生有关(P<0.05),CA、AA基因型的比值比(odds ratio,OR)分别为1.951和1.916,而尚不能认为CYP2C19基因681G/A位点多态性与抗结核药物性肝损伤发生有关。结论 CYP1A2基因734C/A位点多态性与抗结核药物性肝损伤的发生有关,并且携带CA、AA突变基因型的个体是危险人群。
Objective To investigate the relationship between polymorphisms of cytochrome P450 1A2 and 2C19 and anti-TB drug-induced liver injury. Methods A 1: 1 case-control study was conducted in which tuberculosis patients with liver damage caused by anti-tuberculosis drugs were selected as the case group and those without liver injury as the control group, a total of 179 pairs. The genotypes of CYP1A2 gene 734C / A and CYP2C19 681G / A were detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). SPSS17.0 conditional Logistic regression analysis of data. Results The frequency of C allele at CYP1A2 was 37.2%, 62.8%, 47.2% and 52.8% respectively at the 734C / A locus of CYP1A2 gene. The frequencies of G and A alleles at 681G / A of CYP2C19 The frequencies of CYP1A2 gene 734C / A polymorphism were 59.8%, 40.2% and 62.8%, 37.2% respectively in the case group and the control group (P <0.05). The frequencies of CA , Odds ratio (OR) of AA genotype were 1.951 and 1.916, respectively. However, the 681G / A polymorphism of CYP2C19 gene was not related to the occurrence of anti-TB drug-induced liver injury. Conclusion The polymorphism of CYP1A2 gene at 734C / A locus is related to the occurrence of anti-TB drug-induced liver injury. Individuals with CA and AA mutation genotypes are at risk.