The Association Between Genetic Polymorphisms Of Glutathione S-transferases And The Alteration Of Aminotransferases Levels After Transcatheter Arterial Chemotherapy In Hepatocellular Carcinoma Patients

Objective:We investigated the association between the genetic polymorghisms of glutathione S-transferases(GSTM1,GSTT1 and GSTP1)and the alteration of liver function indices after transcatheter arterial chemotherapy (TAC)in hepatocellular carcinoma(HCC)patients,to explore the effect of genetic background of glutathione S-transferases on the hepatotoxicity of chemotherapeutics.Materials and Methods:Polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP)were employed to detect the genic polymorghisms of GSTM1,GSTT1 and GSTP1 Ile313Val in 31 HCC patients from Guangxi,China.And the association between the polymorphisms of GSTs and the alteration of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)levels in these patients after TAC was analyzed.Results:ALT and AST levels in GST-M1 null carriers significantly increased 1-day and 2-day after TAC(P＜0.001).One day after TAC,both ALT and AST levels in GST-T1 carriers were significantly higer than that of GST-T1-null carriers(P=0.030,P=0.027,respectively).There was also significant difference of AST levels among the there time points in GST-T1 carriers(P=0.038).The contribution from GST-P1 genotype to either ALT or AST levels was not significant.There was no statistically significant difference of ALT and AST levels at the three time points between GST-M1(+)/GST-T1(+) and GST-M1(-)/GST-T1(-)haplotypes carriers.However,GST-M1(-)/GST-T1(+) haplotype carriers had higher levels of both ALT and AST after TAC than the GST-M1(+)/GST-T1(-)carriers which is significant at the 3-day time-point (p=0.034 and p=0.036,respectively).The result of multiple linear regression analysis showed:At 1-day and 3-day after TAC,the higher Epirubicin dose administered,the higher ALT and AST levels were.Compared with Han patients,the AST level of Zhuang patients presented a lower level at one day after TAC.with the rising of the HBsAg level for the patients,the AST level decreased at 1-day after TAC.Conclusions:1.GST-M1 null carriers had severe liver damage during TAC therapy than the GST-M1(+)carriers.2.GST-T1 carriers had severe liver damage during TAC therapy than the GST-T1 null carriers..3.If the present observation is validated in a larger sample replication,the carriers of the above deficient genotypes should receive intensive monitering and support during the course of TAC.