Relationship Between Cytochrome P450-2E1 Polymorphisms And The Susceptibility To Antituberculosis Drug-induce Hepatitis

A resurgence of tuberculosis has been recently described in many countries . But the clinical application of antituberculosis was restricted by their adverse reaction ,the most frequent and important is drug induced hepatitis, the antituberculosis drugs such as isoniazid , are metabolized in vivo by enzymatic system, Thus the genetic difference of the enzymatic system is believed to be one of the most important factors in determining susceptibility to drug induced hepatitis, many reports found that P450-2E1,one important enzyme of phase I take part in the metabolism of multiply compounds , the genetic polymorphism of P450-2E1 hase relationship with many diseases such as pulmonary carcinoma, gastric cancer, hepatoma and alcoholic cirrhosis. The aim of this study was to detected the hereditary basis of the tuberculosis drug-induced hepatitis and investigated the pathogenesis and the predisposing factor of it, following jobs were done in our research.1. Blood samples and clinical data from 200 tuberculosis patients in 309 military hospital of PLA were collected, DNA was extracted from each blood sample .2. The frequencies of P450-2E1 Rsa I genotypes were analyzed usingpolymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) , the relationship between the polymorphisms of P450-2E1 Rsa I and the antituberculosis drug-induced hepatitis were analyzed using x2 test.3. Linking with clinical statistics, predisposing factors of antituberculosis drug-induced hepatitis ,such as gender, age, polymorphism of P450-2E1 Rsa I was evaluated by using multivariate logistic regression analysisresults1. The frequencies of P450 — 2E1 Rsal genotypes in all tuberculosis patients, cases and controls were 75.3%, 20%, 4.7% and 61%, 30%, 9% respectively. Statistical difference was found in cases and controls. Polymorphism of P450 — 2E1 Rsal has significant relationship with antituberculosis drug-induced hepatitis risk. The cl/cl genotype is one of the risk factor for antituberculosis drug-induced hepatotoxicity.2. Using multivariate logistic regression analysis, we found that polymorphism of P450-2E1 Rsa I remained a significant independent risk factor for antituberculosis drug-induced hepatotoxicity after adjustment for age, gender and body mass index.