The Association Between Whole Exome Polymorphisms And Alteration Of Serum Alt Levels In Postoperative Hepatocellular Carcinoma Patients Receiving Trans-Hepatic Artery Chemotherapy

OBJECTIVE:Serum alanine aminotransferase level is an important indicator for the detection and evaluation of liver function. Detect the SNP loci closely related with the serum alanine aminotransferase level in hepatocellular carcinoma patients who received trans-hepatic artery chemotherapy treatment, and research the genetic variation model of liver function damage induced by TAC treatment for the HCC patient.METHODs:We collected 59 liver cancer tissue specimens, and extract the DNA from the specimens in order to acquire the genetic information. Then we performed DNA chip by the extracted DNA.Through microarray analysis and genome-wide association study, we detected a number of SNPs which is-closely related with the serum alanine aminotransferase level in HCC patients who received the triple-drug-therapy TAC treatment. A quality control standard was performed to limit the SNPs with statistical significance.RESULTS:The association analysis showed that rs2306283 (located in SLCO1B1, P=3.65×10-5) was significantly associated with the serum alanine aminotransferase level in HCC patients who received TAC treatment. The genetic model of rs2306283 is a dominant model (AA+AG VS. GG,P=0.039, OR=0.547,95%CI=0.308-0.970).Conclusions:This study demonstrates that an exon variant (rs2306283) in SLCO1B1 has a close association with the serum alanine aminotransferase level in HCC patients who received TAC treatment, and the liver function of patients who carry AA genotype and AG genotype are more likely to be abnormal than those who carry GG genotype. Therefore, more attention should be paid in the course of clinical treatment, and this study will provide gist for clinical individual dosage with the development of the technology of gene screening.