Study of the relationship between polymorphisms of cytochrome P450 2E1 and antituberculosis druginduced hepatic injury
10.3760/cma.j.issn.1000-6680.2010.12.010
- VernacularTitle:细胞色素P45O 2E1基因多态性与抗结核药物致肝损伤的关系
- Author:
Yi CHEN
;
Mei GUO
;
Shiming LI
;
Peng ZHANG
;
Jinqi HAO
;
Bing ZHANG
;
Guiyu TANG
;
Jianping ZHOU
;
Fumin FENG
- Publication Type:Journal Article
- Keywords:
Antitubercular agents;
Hepaticis,toxic;
Polymorphism,genetic;
Cytoohrome P450 CYP 2E1
- From:
Chinese Journal of Infectious Diseases
2010;28(12):748-752
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether the gene polymorphisms of cytochrome P450(CYP) 2E1 are associated with the risk of anti-tuberculosis drug induced hepatotoxity (ADIH).Methods In this case control study, 339 patients who matched the diagnosis criteria of tuberculosis were included. The gcneral healthy status and liver biochemical parameters were checked in all these patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) technique was used to determine CYP 2Et polymorphisms. The statistic analysis were performed by using both univariate and multivariate Logistic regression analysis. Results The allele frequencies of CYP 2E1 7632T/A, 1019C/T and 1259G/C in 103 tuberculosis patients of ADIH group were 17.5%, 26.2%and 27.2 % respectively, while those in 236 tuberculosis patients of control group were 29.7 % ,39.4 %and 40.7%, respectively (x2 =5.539, P＜0.05; x2 =5.458, P＜0.05; x2 =5.628, P＜0.05). The results of univariate analysis demonstrated that the risk of concurrent ADIH was significantly higher in patients with wild genotypes of CYP 2E1-7632T/A, CYP 2E1-1259G/C, CYP 2E1-1019C/T than in patients with other genotypes. After adjusted for sex, occupation and alcohol consumption status, the results of multivariate Logistic regression analysis also showed that wild genotypes of CYP 2E1-7632T/A, CYP 2El-1259G/C, CYP 2E1-1019C/T were significantly associated with higher risk of ADIH. The results of interaction analysis indicated that the wild genotypes of CYP 2E1-7632T/A and CYP 2E1-1259G/C or CYP 2E1-1019C/T had synergetic effects on the development of ADIH.Conclusions The risk of concurrent ADIH is significantly higher in patients with wild genotypes of CYP 2E1-7632T/A, CYP 2E1-1259G/C, CYP 2E1-1019C/T compared to patients with othergenotypes. Wild genotypes of CYP 2E1-7632T/A and CYP 2E1-1259G/C or CYP 2El-1019C/T have synergetic effects on the development of ADIH.
