乙型肝炎肝硬化中医证型与TANK基因单核苷酸多态性的关联

Associations of rs3820998 polymorphism in TANK gene with syndrome types of TCM of hepatitis B related cirrhosis

目的:探讨TANK(the tumor necrosis factor receptor family associated factor family member-associated NF-κBactivator,TANK)基因的单核苷酸多态性(single nucleotide polymorphism,SNP)与乙型肝炎肝硬化中医证型的关联。方法:运用Taqman MGB探针聚合酶链反应(PCR)检测224例乙肝病毒无症状携带者(AsC组)和260例乙型肝炎肝硬化患者(LC组)TANK基因rs3820998位点的多态性并进行基因分型,分析其基因型和等位基因频率的分布,以及与乙型肝炎肝硬化中医证型之间的关系。结果:TANK基因rs3820998位点AsC组中G/G、G/T、T/T基因型频率分别为57.6%,33.9%,8.5%,与LC组中基因型频率分布比较差异有显著性意义(P<0.05)。AsC组中G等位基因频率为68.3%,与LC组比较差异无显著性意义(P>0.05)。在隐性模型中,T/T基因型进展为肝硬化的风险降低,与G/G+G/T型相比差异有显著性意义(OR=0.430,95%CI:0.195～0.991,P=0.034)。继续分层研究显示湿热中阻、肝郁脾虚和瘀血阻络型患者T/T基因型进展为肝硬化的风险较G/G+G/T基因型患者降低,差异有显著性意义(湿热中阻OR=0.462,95%CI:0.253～0.913;肝郁脾虚OR=0.319,95%CI:0.216～0.881;瘀血阻络OR=0.268,95%CI:0.140～0.805;均P<0.05),而肝肾阴虚和脾肾阳虚患者中TANK rs3820998位点多态性与乙型肝炎肝硬化临床转归无显著性相关(P>0.05)。结论:TANK rs3820998位点基因型频率分布在AsC组和LC组中比较差异有显著性意义,而等位基因频率分布差异则无显著性意义,T/T基因型在湿热中阻、肝郁脾虚和瘀血阻络的患者中,是肝硬化进展的防护性因素,而肝肾阴虚和脾肾阳虚患者中T/T基因型可能与其肝硬化进展无相关性。

Objective： To determine the correlation between TANK （the tumor necrosis factor receptor family associated factor family member-associated NF-KB activator） single nucleotide polymorphism （SNP） and syndrome types of TCM of hepatitis B related cirrhosis. Methods： Two hundred and twenty-four asymptomatic carriers of hepatitis B virus and 260 patients with hep- atitis B related cirrhosis were enrolled as AsC group and LC group. Rs3820998 polymorphisms in TANK gene were detected by polymerase chain reaction （PCR） with Taqman MGB probe in both groups. Gene types , distribution of allele frequency and re- lation with syndrome types of TCM were analyzed. Results： For rs3820998 in TANK gene, there were statistical differences in the distribution of allele G/G, G/T and T/T between AsC and LC group （P 〈 0. 05 ）, while no significant difference was found in gallele frequency between two groups （P 〉 0. 05） . In recessive model the risk of T/T genetype progressing to liver cirrhosis was decreased and had significant difference between G/G ＋ G/T genetype （OR = 0. 430, 95% CI： O. 195 -0. 991, P = 0. 034） . In patients of damp-heat blocking in spleen and stomach type, liver-depression and spleen-deficiency type, obstruction of collaterals by blood stasis type the risk of T/T genetype progressing to liver cirrhosis was decreased and had significant differ- ence between G/G ＋ G/T genetype （ OR = 0. 462, 95% CI： O. 253 - 0. 913 ; OR = 0. 319, 95% CI： O. 216 - 0. 881 ; OR = 0. 268, 95% CI： O. 140 - 0. 805 respectively; P 〈 0.05）, while in patients of Yin deficiency of liver and kidney and Yang de- ficiency of spleen and kidney rs3820998 in TANK gene had no correlation with clinical sequelae of hepatitis B related cirrhosis （P 〉 0. 05 ） . Conclusion ： The genetype of rs3820998 in TANK gene had significant difference between AsC group and LC group, while allele frequency was found no significant difference. In patients of damp-heat blocking in spleen and stomach type, liver-depression and spleen-deficiency type, obstruction of collaterals by blood stasis type T/T genetype was protective factor for liver cirrhosis progressing, while in patients of Yin deficiency of liver and kidney and Yang deficiency of spleen and kidney it had no correlation with progress to liver cirrhosis.