CYP1A1和GSTP1基因多态性与抗结核药物性肝损伤的关系  

Study on the relationship between the gene polymorphisms of cytochrome P450 1A1 or glutathione transferase P1 and anti-tuberculosis drug-induced liver injury

作　　者：贺蕾[1] 高丽[1] 史哲[1] 李世明[2] 张朋[2] 郑国颖[1] 李云[1] 胡泊[1] 冯福民[1] 

机构地区：[1]河北联合大学公共卫生学院河北省煤矿卫生与安全重点实验室,河北唐山063000 [2]唐山市结核病医院检验科,河北唐山063000

出　　处：《中国临床药理学杂志》2015年第4期243-246,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81041096);唐山市重点实验室基金资助项目(08150201A-1-8)

摘　　要：目的分析细胞色素P450 1A1(CYP1A1)和谷胱甘肽转移酶P1(GSTP1)基因多态性与抗结核药物性肝损伤(ADLI)的相关性。方法抗结核治疗致肝损伤的结核病患者127例为病例组,127例无肝损伤者为对照组,收集其环境因素暴露资料及静脉血。CYP1A1基因Msp I位点和GSTP1基因Ile105 Val位点多态性检测用聚合酶链反应限制性片段长度多态法(PCR-RFLP)。用SPSS17.0软件对环境因素和基因型进行单因素和多因素条件Logistic回归分析。结果 CYP1A1基因Msp I位点各基因型在2组间的分布差异无统计学意义;GSTP1基因Ile105Val位点AA、AG、GG基因型在病例组和对照组频率分别为55.91%,32.28%,11.81%和70.08%,26.77%,3.15%,GG基因型在2组分布差异有统计学意义(P<0.05)。GG基因型的危险度比值比(OR)值为4.701。单因素条件Logistic回归分析发现,饮酒为ADLI的危险因素;多因素分析中调整饮酒因素的影响后,GSTP1基因Ile105 Val位点GG基因型仍为ADLI的危险基因型。结论 GSTP1基因Ile105 Val位点多态性与ADLI的发生有关,携带GG基因型的个体是危险人群。Objective To retrospectively investigate the relationship between the gene polymorphisms of cytochrome P450 1A1 ／ glutathione transferase P1（ CYP1A1 or GSTP1） and anti- tuberculosis drug-induced liver injury（ ADLI）. Methods Total 127 cases and 127 controls were collected in 1∶ 1 match. Their exposure data of data and blood samples were collected. The genotypes were detected by polymerase chain reaction and restriction fragment length polymorphism technique（ PCR- RFLP） method SPSS 17. 0 software was used to do Logistic regression analysis on environmental factors and genotype univariate and multivariate analysis. Results The allele frequencies of gene CYP1A1 genes in two groups had no statistical difference. While the frequencies of AA,AG and GG genotypes at Ile105 Val site of GSTP1 gene were55. 91%,32. 28%,11. 81% in case group and 70. 08%,26. 77%,3. 15% in control group. The analysis demonstrated that the frequencies of GSTP1 gene Ile105 Val genotypes in case group were significantly higher than those in control group（ P〈0. 05）. Univariate Logistic regression analysis showed that alcohol was the risk factor of ADLI,andafter the regulation of certain factor in multivariate analysis,the GG genotype at Ile105 Val site of GSTP1 gene was still the risk factor of ADLI. Conclusion The polymorphim of Ile105 Val site of GSTP1 gene is correlated with the occurrence of ADLI and GG carriers are considered as risk population.

关 键 词：细胞色素P450 1A1 谷胱甘肽转移酶P1 抗结核药 肝损伤 多态性 

分 类 号：R52[医药卫生—内科学] R181.3[医药卫生—临床医学]