CAJ | 학술논문

目的探讨细胞色素P450(CYP)2E1基因多态性与抗结核药物所致肝损伤(ADIH)的关系.方法采用病例对照研究设计,选择符合条件的339例结核患者为研究对象,调查其一般情况及肝功能,聚合酶链反应-限制性片段长度多态性分析进行基因分型.数据行单因素和多因素Logistic回归分析.结果 ADIH病例组103例结核患者CYP 2E1的7632T/A、101 9C/T、1259G/C等位基因频率分别为17.5%、26.2%和27.2%,对照组236例结核患者分别为29.7%、39.4%和40.7%(x2=5.539,P＜0.05;x2=5.458,P＜0.05;x2=5.628,P＜0.05).经多因素Logistic回归分析调整了性别、职业、饮酒等危险因素后,7632T/A、1019C/T、1259G/C位点多态性与ADIH的发生仍有相关性,且7632T/A与1019C/T及1259G/C位点野生基因型在ADIH发生过程中起协同作用.结论携带CYP 2 E1的7632T/A、1019C/T和1259G/C位点野生基因型的个体发生ADIH的危险性增高,且在ADIH的发病过程中起协同作用.
목적 탐토세포색소P450(CYP)2E1기인다태성여항결핵약물소치간손상(ADIH)적관계.방법 채용병례대조연구설계,선택부합조건적339례결핵환자위연구대상,조사기일반정황급간공능,취합매련반응-한제성편단장도다태성분석진행기인분형.수거행단인소화다인소Logistic회귀분석.결과 ADIH병례조103례결핵환자CYP 2E1적7632T/A、101 9C/T、1259G/C등위기인빈솔분별위17.5%、26.2%화27.2%,대조조236례결핵환자분별위29.7%、39.4%화40.7%(x2=5.539,P＜0.05;x2=5.458,P＜0.05;x2=5.628,P＜0.05).경다인소Logistic회귀분석조정료성별、직업、음주등위험인소후,7632T/A、1019C/T、1259G/C위점다태성여ADIH적발생잉유상관성,차7632T/A여1019C/T급1259G/C위점야생기인형재ADIH발생과정중기협동작용.결론 휴대CYP 2 E1적7632T/A、1019C/T화1259G/C위점야생기인형적개체발생ADIH적위험성증고,차재ADIH적발병과정중기협동작용.
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.