肝细胞癌切除术后行经导管肝动脉灌注化疗术患者ALT水平改变相关的单核苷酸多态性位点分析  

Analysis on single nucleotide polymorphism loci related to ALT level variation in patients undergoing trans-hepatic artery chemotherapy after resection for hepatocellular carcinoma

作　　者：陈治伟[1] 刘晓光[1] 韩创业 朱广志[1] 苏浩[1] 于龙[1] 鲁磊[1] 廖锡文[1] 覃玮[1] 杨成昆 刘征涛[1] 叶新平[1] 李佳荃[2] 桂滢[2] 莫曾南[2] 胡艳玲[2] 肖开银[1] 彭涛[1] 

机构地区：[1]广西医科大学第一附属医院肝胆外科,南宁市530021 [2]广西医科大学,南宁市530021

出　　处：《广西医学》2016年第12期1629-1633,共5页Guangxi Medical Journal

基　　金：国家自然科学基金(81560535,81072321,30760243,30460143,30560133);2009年教育部新世纪优秀人才支持计划(NCET);广西科学研究与技术开发计划项目(桂科攻1104003A-7);广西医疗卫生重点科研课题(重201018)

摘　　要：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.

关 键 词：原发性肝细胞癌 经肝动脉化疗术 谷丙转氨酶 单核苷酸多态性 全基因组关联分析 

分 类 号：R342.4[医药卫生—基础医学]