IL-2基因rs2069763、IL-10基因rs1800872位点多态性与乙肝相关性肝癌的相关性研究

发布时间：2018-03-18 17:39

  本文选题：乙肝相关性肝癌　切入点：白细胞介素-2　出处：《大连医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景及目的乙型肝炎病毒(HBV)相关性肝细胞癌(HCC)是一个复杂的、由多种基因及环境因素参与的多步骤过程。在中国,约有90%的肝癌患者合并有HBV感染的背景。肝癌的发生与炎症、免疫等多种因素相关,HBV感染后,病毒长期复制活动引起肝脏慢性炎症,刺激血管的再生、损伤DNA、刺激恶性肿瘤细胞的生长等导致肿瘤发生,但具体的机制尚不清楚。单核苷酸多态性(SNP)是影响个体遗传易感性的重要因素。目前有关白细胞介素-2(IL-2)SNP和白细胞介素-10(IL-10)SNP对HBV相关性HCC发病风险的相关性的研究观点不一。本研究选取IL-2基因rs2069763位点及IL-10基因rs1800872位点,探究这2个位点与HBV相关性HCC遗传易感性的关系,并进一步探讨两基因位点之间是否存在交互作用。方法本研究自2014年11月至2016年8月期间,于青岛市市立医院选取HBV相关性HCC的患者263例(男性216例)作为病例组,健康者350例(男性284例)作为对照组。收集受试者的血液标本,通过多聚酶链反应(PCR)及飞行时间质谱方法(MALDI-TOF MS)检测IL-2rs2069763、IL-10 rs1800872的基因型。同时收集受试者的一般资料、临床资料及实验室检查指标,利用SPSS 19.0统计软件,用Pearson χ2检验、t检验及Logistic回归分析等方法对各组基因型、基因位点及临床资料等进行分析。用广义多因子降维软件(GMDR)测IL-2基因SNP rs2069763位点和IL-10基因SNP rs1800872之间的交互作用。结果HBV相关性HCC组与对照组相比,在性别、年龄、饮酒史、吸烟史方面的差异无统计学意义(P0.05)。病例组血清总蛋白和白蛋白指标明显低于对照组(P0.01),而血清总胆红素、直接胆红素、间接胆红素、谷丙转氨酶、谷草转氨酶(AST)、碱性磷酸酶(ALP)及谷氨酰转肽酶(GGT)水平明显高于健康对照组(P0.01)。IL-2基因rs2060763位点、IL-10基因rs1800872位点的基因型和等位基因的频率分布在病例组和对照组之间的差异具有统计学意义(P值均0.05)。Rs2069763G等位基因和rs1800872G等位基因可以明显增加HBV相关性 HCC 的发病风险(分别为:OR,1.541,95%CI,1.053 to 2.256,P=0.026,OR,1.402,95%CI,1.011 to 1.943,P=0.043)。在调整了混杂因素年龄、性别、饮酒及吸烟后,logistics回归显示这种差异依然具有统计学意义(分别为OR,1.605,95%CI,1.090 to 2.364,P=0.005;OR,1.465,0.579,95%CI,1.052 to 2.041,P=0.006)。在HBV相关性HCC组中,与非携带者相比,IL-2基因rs2069763位点G等位基因携带者具有更高的AST水平(P = 0.001)和更高的ALP水平(P0.001);IL-10基因中rs1800872的G等位基因携带者的ALT(P = 0.020)、AST(P = 0.011)和ALP(P = 0.024)的水平更高.GMDR软件测交互性作用分析显示IL-2基因rs2069763和IL-10基因rs1800872两个位点之间无交互作用(P0.05),提示两位点联合作用时并不能对HBC相关性HCC的发病风险产生影响。结论在中国青岛地区汉族人群中,IL-2rs2069763G等位基因及IL-10rs1800872 G等位基因可以增加HBV相关性HCC的发病风险。IL-2基因rs2069763位点及IL-10基因rs1800872位点之间对HBV相关性HCC易患性的影响无交互作用。
[Abstract]:Background and objective: hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is a complex, multi-step process involved by multiple genetic and environmental factors. In Chinese, about 90% of patients with primary hepatocellular carcinoma with HBV infection and inflammation of liver cancer. The background, immune and other factors related to HBV infection. After long-term virus replication activity caused by chronic liver inflammation, regeneration, stimulation of vascular injury DNA, stimulation of malignant tumor cell growth and tumorigenesis, but the mechanism is not clear. The single nucleotide polymorphism (SNP) is an important factor affecting the individual genetic susceptibility. The interleukin -2 (IL-2) SNP and interleukin -10 (IL-10) SNP on HBV research point of view correlation correlation between HCC risk is not one. This study selected IL-2 rs2069763 gene and IL-10 gene rs1800872 locus, explore the 2 loci associated with HBV HCC. The relationship between transfer susceptibility, and to further explore the interaction between the two loci. The research method from November 2014 to August 2016, in the Qingdao municipal hospital selected the HBV Association of HCC in 263 patients (216 males) as the case group, 350 healthy subjects (284 males) collected by blood as the control group. Samples that subjects by polymerase chain reaction (PCR) and time of flight mass spectrometry (MALDI-TOF MS) to detect IL-2rs2069763 genotype IL-10 rs1800872. The general data were collected simultaneously, clinical data and laboratory examination indexes, using the statistical software SPSS 19, 2 Pearson x t test, Logistic test and regression analysis the methods of each genotype, gene loci and clinical data were analyzed. By using generalized multifactor dimensionality reduction (GMDR) software test of IL-2 gene and IL-10 gene loci SNP rs2069763 SNP rs1800872. The interaction of HBV. Results the correlation between HCC group compared with control group in gender, age, history of drinking, no statistically significant difference between the smoking history (P0.05) cases. The serum total protein and albumin index was significantly lower than the control group (P0.01), serum total bilirubin, direct bilirubin, indirect bilirubin, alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) levels were significantly higher than that of the control group (P0.01.IL-2) rs2060763 gene, the difference was statistically significant genotype frequency distribution of IL-10 gene rs1800872 locus and allele between case group and control group (P 0.05).Rs2069763G allele and rs1800872G allele could significantly increase the risk of HBV associated HCC (OR, 1.541,95%CI, 1.053 to 2.256, P=0.026, OR, 1.402,95%CI 1.011, to 1.943, P=0.043). After adjustment The confounding factors of age, sex, drinking and smoking, logistics regression analysis showed that the difference has statistical significance (OR, 1.605,95%CI 1.090, to 2.364, P=0.005; OR, 1.465,0.579,95%CI 1.052, to 2.041, P=0.006). The correlation between HBV in the HCC group, compared with non carriers of IL-2 gene rs2069763 allele G carriers have higher AST levels (P = 0.001) and higher levels of ALP (P0.001); rs1800872 IL-10 gene in the G allele of ALT (P = 0.020), AST (P = 0.011) and ALP (P = 0.024) of the higher level of.GMDR software test analysis showed that the interaction effect between IL-2 gene rs2069763 and IL-10 gene rs1800872 two loci interaction (P0.05), the influence that joint action of the two sites and not on the risk of HBC related HCC. Conclusion the Han population in Qingdao area Chinese, IL-2rs2069763G allele And IL-10rs1800872 G allele can increase the risk of HBV related HCC. There is no interaction between the.IL-2 gene rs2069763 locus and IL-10 gene rs1800872 locus on HBV related HCC vulnerability.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62;R735.7
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本文编号：1630622