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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 investigate the single nucleotide polymorphisms (SNPs) associated with the changes of serum ALT levels in patients undergoing transcatheter arterial chemoembolization (TAC) after resection of primary hepatocellular carcinoma (PHC). Methods Fifty-nine patients with PHC treated with TAC after hepatectomy for hepatectomy were enrolled, and their tissues were harvested to extract tissue DNA. All-exon SNPs were obtained by microarray technique. Multivariate analysis was used to select the SNP loci associated with postoperative ALT / preoperative ALT. Candidate SNP sites were screened by the KOBAS 2.0 program database, and linear regression models were used to analyze the genotypes that affected the postoperative ALT changes. Results The results of KOBAS 2.0 program showed that rs2306283 located on chromosome 12 SLCO1B1 was associated with an increased ALT / preoperative ALT (minimum allele frequency = 0.132, P = 3.65 × 10 -5) . The linear regression analysis showed that the AA + AG genotype of SLCO1B1 gene was 2.55 (P <0.05), rs2306283 was a dominant genetic model, and the AA genotype and AG genotype were risk genotypes relative to GG genotype. Conclusions AA and AG genotypes of rs2306283 in SLCO1B1 gene after TCC resection in hepatocellular carcinoma patients may be related to postoperative ALT levels.