目的 探讨影响原发性肝细胞癌(PHC)切除术后行经导管肝动脉灌注化疗术(TAC)患者血清ALT水平变化相关的单核苷酸多态性(SNP)位点。方法 纳入肝癌肝切除术后行TAC治疗的PHC患者59例,获取其术中切取标本以提取组织DNA,通过芯片技术获取全外显子SNP。通过EMMAX检验多因素分析选择与术后ALT/术前ALT比值相关的SNP位点。通过KOBAS 2.0 program数据库筛选有关的候选SNP位点,采用线性回归模型分析影响患者术后ALT变化的基因型。结果 KOBAS 2.0 program筛选结果显示,位于12号染色体SLCO1B1基因上的rs2306283与患者术后ALT/术前ALT比值升高相关(最小等位基因频率=0.132,P=3.65×10~(-5))。线性回归分析结果显示,相对于GG基因型,SLCO1B1基因的AA+AG基因型OR=2.55(P〈0.05),rs2306283为显性遗传模型,AA基因型和AG基因型为风险基因型。结论 肝细胞癌切除术后行TAC患者SLCO1B1基因rs2306283的AA和AG基因型可能与术后ALT水平升高相关。
Objective To explore the single nucleotide polymorphism(SNP) loci related to the serum ALT level variation in patients undergoing trans-catheter arterial chemotherapy (TAC) after resection for primary hepatocellular carcinoma( PHCC ). Methods Fifty-nine patients with PHCC who underwent TAC after resection for liver cancer were enrolled, and their DNAs were extracted from the specimens obtained in surgical resection. The SNPs of whole exons were acquired using DNA chips technology. The SNP loci related to postoperative ALT/preoperative ratio were selected by EMMAX multivariate analysis. The relative candidate SNP loci were screened by KOBAS 2.0 program database. The genotypes influencing postoperative ALT variation of the patients were analyzed by linear regression analysis. Results The result screened by KOBAS 2.0 program showed that rs2306283 located in SLCO1 B1 gene of chromosome12 was related to elevated postoperative ALT/preoperative ratio( minor allele frequency = 0. 132, P = 3.65 × 10 -5 ). The resuh of linear regression analysis showed that OR value of SLCO1B1 gene AA + AG genotype was 2.55 (P 〈 0.05 ) , rs2306283 was a dominant model, and AA and AG genotypes were risk genotypes. Conclusion For patients underwent TAC after resection for PHCC, AA genotype and AG genotype of SLCO1B1 gene rs2306283 are probably associated with the elevation of postoperative ALT level.