生存素基因与华东汉族人群原发性肝细胞癌的相关性研究
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Correlation of survivin gene with hepatocellular carcinoma in Han nationality in east China
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    \[摘要\]目的探讨华东汉族人群中生存素(survivin)基因与原发性肝细胞癌(HCC)的相关性。方法采用病例对照研究,在江苏省海门市收集176例HCC病例和196例健康对照。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对survivin基因的rs9904341和rs1042489两个位点进行基因分型,在不同的遗传模式下分别分析rs9904341和rs1042489位点的基因型及其单倍型与HCC的关系。结果单因素分析表明,在不同的遗传模式下,rs9904341及rs1042489两个位点的基因型及等位基因分布在HCC病例组及对照组间的差异均无统计学意义。连锁不平衡(LD)分析发现,rs9904341与rs1042489两个位点间存在LD(χ2=4.777,P=0.03),HCC病例组及对照组中两个位点的连锁不平衡常数D’分别为0.188和0.183。采用多因素Logistic回归分别在不同的遗传模式下进行单倍型分析,根据赤池信息量准则(AIC)值最小原则筛选出隐性遗传模式下的模型为最优模型,在隐性遗传模式下,控制饮酒、乙肝史等因素后,以不具有rs9904341C-rs1042489T(C-T)单倍型为参照,具有C-T单倍型者HCC的发病风险下降(OR=0.48,P=0.04),未发现其他与HCC有关的单倍型;多因素分析还显示HBsAg+及乙肝史为HCC的危险因素,但未发现单倍型与环境因素的交互作用。结论在华东汉族人群中,未发现survivin基因的rs9904341及rs1042489位点多态性与HCC的发病有关,但rs9904341C-rs1042489T单倍型可能是HCC的保护单倍型。

    Abstract:

    \[Abstract\]ObjectiveTo explore the association of survivin gene with hepatocellular carcinoma(HCC) in Han nationality in east China. MethodsA case-control study was designed, which included 176 HCC cases and 196 healthy controls, all from Haimen city of Jiangsu province. The rs1042489 and rs9904341 loci of survivin gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and the association of the genotypes and haplotypes of the two loci with HCC was analyzed under different genetic models. ResultsUnivariate analysis showed no significant difference in the genotypes or allele distribution between HCC case group and the control group under different genetic models in either rs9904341 or rs1042489 loci (P>0.05). Linkage disequilibrium (LD) analysis showed that the two loci were in LD (χ2=4.777,P=0.03), with the D’ value being 0.188 and 0.183 in the case and control group, respectively. The recessive genetic model was found to be the optimal model by multivariate Logistic regression, according to the lowest value of Akaike’s information criteria (AIC). With no rs9904341C-rs1042489T (C-T) haplotype as reference, it was found that the haplotype of C-T from the two loci was associated with a lower risk for HCC under the recessive genetic model, with the factors such as alcohol drinking and HBV infection controlled (OR=0.48, P=0.04), and no other haplotypes were found associated with HCC. Multivariate analysis showed that HBsAg+ and hepatitis B were the risk factors for HCC, but without haplotype-environment interaction. ConclusionNo association has been found for rs9904341 or rs1042489 in survivin gene with HCC in Han nationality in east China, and rs9904341C-rs1042489T might be a protective haplotype for HCC.

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  • 收稿日期:2010-06-11
  • 最后修改日期:2010-11-14
  • 录用日期:2010-11-19
  • 在线发布日期: 2010-12-21
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