细胞色素P450 1A2和2C19基因多态性与抗结核药物性肝损伤的关系

 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。

Relationship Study between the Gene Polymorphisms of Cytochrome P450 1A2/2C19 and Anti-Tuberculosis Drug-Induced Hepatic Injury

OBJECTIVE To investigate the relationships between the gene polymorphisms of cytochrome P450(CYP)1A2/2C19 and anti-tuberculosis drug-induced hepatic injury. METHODS A 1∶1 matched case-control study was conducted, with 179 cases and 179 controls were collected in patients who received anti-tuberculosis therapy, the matching conditions were that of same gender, age difference is less than 5 years old, and using a similar chemotherapy regimen. The genotypes of CYP1A2/CYP2C19 genes were detected by polymerase chain reaction and restriction fragment length polymorphism technique(PCR-RFLP). The statistic analysis were performed by using both univariate and multivariate Logistic regression analysis. RESULTS The allele C/A frequencies of CYP1A2 gene and allele G/A frequencies of CYP2C19 gene in case groups were37.2%, 62.8% and 59.8%, 40.2%; while in control groups were 47.2%, 52.8% and 62.8%, 37.2%. The analysis demonstrated that the frequencies of CYP2C19 gene 681G/A genotypes in cases and controls were not statistically significant, while the CYP1A2 gene 734C/A genotypes in cases were significantly different from that in controls, after multivariate analysis, ADIH remained associated with CYP1A2 gene CA/AA genotypes after adjusting for BMI and drinking status, the adjusted OR were 1.951 and 1.916.CONCLUSION The risk of concurrent ADIH is significantly higher in patients with CA, AA genotypes of CYP1A2 gene 734C/A site.