摘要
目的:研究CYP3A5酶基因多态性与双环醇降酶、抗病毒、抗肝纤维化等临床效应个体差异的相关性,以指导临床个体化用药。方法:34例慢性乙型肝炎患者在常规治疗的基础上口服双环醇片(25 mg,tid)治疗,疗程24周,治疗前后检测肝功能(ALT,AST)、乙肝病毒学指标(HBeAg,HBeAb,HBsAg,HBV-DNA)、肝纤维化指标[透明质酸(HA)、层黏连蛋白(LN)、血清Ⅲ型前胶原肽(PⅢP)和Ⅳ型胶原(Ⅳ-C)]。采用聚合酶链反应扩增及限制性片段长度多态性(PCR-RFLP)技术对患者CYP3A5酶基因进行分型。结果:按CYP3A5基因型分组,CYP3A5*1组16例(包括CYP3A5*1/*1型2例和CYP3A5*1/*3型14例),CYP3A5*3组(即CYP3A5*3/*3型)18例。治疗后,两组患者ALT和AST水平均显著下降(P<0.05);CYP3A5*3组患者的ALT和AST下降幅度分别为79.73%和74.76%,显著大于CYP3A5*1组的65.90%和49.63%(P<0.05);CYP3A5*3组ALT复常率和AST复常率均显著高于CYP3A5*1组(P<0.05);CYP3A5*1组HBV-DNA阴转率、HBeAg阴转率、HBeAg血清转换转率分别为12.5%,6.25%和6.25%,低于CYP3A5*3组的22.22%,16.67%和11.11%,但差异均无统计学意义(P>0.05);两组血清肝纤维化指标HA,LN和PⅢP均显著下降(P<0.05),CYP3A5*3组下降的幅度均大于CYP3A5*1组。结论:CYP3A5酶基因型可能对双环醇治疗慢性乙肝的临床疗效产生一定影响,基因型为CYP3A5*3的慢性乙肝患者双环醇疗效反应较强,该酶基因型可能成为双环醇疗效(尤其是降酶效应)的预测因子。但因样本量相对较少,最终结论尚需在更大样本量的研究中加以确认。
Objective： To investigate the relationship between the genetic polymorphisms of CYP3A5 and the clinical effectiveness of bicyclol in patients with chronic hepatitis B for establishing possible individual medication. Methods： Patients with chronic hepatitis B （n = 34） were treated with bicyclol tablets for 24 weeks in addition to general treatments. For each patient, liver function index （ ALT and AST） , hepatitis B virus markers （HBeAg, HBeAb, HBsAg and HBV-DNA） and the markers of hepatic fibrosis （HA, LN, PⅢP and Ⅳ-C） were determined before and after the treatment. The CYP3A5 genotyping of each patient was determined by the PCRRFLP analysis. Results： Patients were divided into CYP3A5 ＊ 3 （n = 18） and CYP3A5 ＊ 1 carriers （n = 16） based on the genotypes of CYP3A5 ＊ 3 gene. The CYP3A5 ＊ 1 carriers included CYP3A5 ＊ 1/＊ 1 （n =2） and CYP3A5 ＊ 1/＊ 3 （n = 14）. Serum ALT and AST levels were obviously decreased after the treatment in all patients. The ALT and AST levels reduced significantly greater （P 〈 0. 05） in CYP3A5 ＊ 3 carriers （79. 73% and 74.76% ） than in CYP3A5 ＊ 1 carriers （65.90% and 49.63% ）. The recovery rates of ALT and AST were significantly higher in CYP3A5 ＊ 3 carriers than in CYP3A5 ＊ 1 carriers （P 〈 0.05）. HBV-DNA negative conversion rate, HBeAg negative conversion rate and HBeAg sero-conversion rate in CYP3A5 ＊ 1 carriers were 12.50% , 6.25% and 6.25% respectively, which were lower than those in CYP3A5 ＊ 3 carriers （22.22% , 16.67% and 11.11% ） but the differences were not statistically significant （P 〉 0.05 ）. After treatment, the serum HA, LN and Pill P levels were significantly reduced （P 〈 0.05） , and the reduction was greater in CYP3A5 ＊ 3 carriers than in CYP3A5 ＊ 1 carriers. Conclusion： CYP3A5 genotype has an impact on the therapeutic effects of bicyclol on liver function and the virus. Bicyclol is more effective in CYP3A5 ＊ 3 carriers than in CYP3A5 ＊ 1 carriers. CYP3A5genotyping may be helpful in predicting therapeutic effects of bicyclol especially for decreasing ALT and AST. Further clinical evaluations using larger size of samples are necessary to verify this assumption.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2008年第4期329-332,共4页
Chinese Journal of New Drugs
