基于GWAS的lncRNA遗传变异与HBV感染结局的关联研究

发布时间：2018-03-15 06:13

本文选题：HBV相关肝癌　切入点：lncRNA　出处：《广东药科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:分析基于GWAS的lnc-ACACA-1和lnc-RP11-150O12.3.1-1遗传变异对HBV感染结局影响的单独作用及基因-环境交互作用。方法:基于乙肝相关肝癌的全基因组关联研究(genome-wide association study,GWAS)文献,提取与乙肝相关肝癌有显著关联的SNP(single nucleotide polymorphism),根据SNP间的连锁不平衡确定研究区域,在这些区域查找有潜在功能的lncRNA SNP,最终筛选出2个lncRNA(lnc-ACACA-1和lnc-RP11-150O12.3.1-1)上的7个SNP(rs7221955、rs9891142、rs11776545、rs2275959、rs2298320、rs2298321、rs1008547)。以554例HBV自限清除、552例慢性乙肝患者(chronic hepatitis B patients,CHB)和644例乙肝相关肝癌患者(hepatocellular carcinoma,HCC)为研究对象,采用病例对照研究,应用多分类logistic回归模型与多因子降维法相结合的策略,系统分析单位点、基因-环境交互作用对HBV感染结局的影响。结果:1.在环境因素分析中,吸烟、饮酒、肿瘤家族史均是HBV慢性感染及HBV相关肝癌发病的危险因素(吸烟,OR=7.67,95%CI=5.82-10.12;饮酒,OR=6.24,95%CI=0.19-0.32;肿瘤家族史,OR=4.63,95%CI=3.20-6.73)。2.以HBV自限清除组为对照,CHB组为病例,发现rs7221955和rs9891142与年龄有相乘和相加的交互作用,且年龄大于60岁的个体携带rs7221955 C等位基因或rs9891142 C等位基因可以增加HBV慢性感染的风险(rs7221955,OR=1.84,95%CI=1.06-3.21;rs9891142,OR=1.78,95%CI=1.03-3.10)。3.以HBV自限清除组为对照,HCC组为病例,发现rs7221955与年龄有相加的交互作用,且年龄大于60岁的个体携带rs7221955 C等位基因或rs9891142 C等位基因可以增加HBV相关肝癌的发病风险(rs7221955,OR=1.82,95%CI=1.05-3.16;rs9891142,OR=1.80,95%CI=1.04-3.10),同时携带CC单体型也可增加HBV相关肝癌的发病风险(OR=1.32,95%CI=1.02-1.70)。4.以CHB组为对照,HCC组为病例,发现rs11776545、rs2275959、rs1008547与肿瘤家族史有相乘和相加的交互作用,且有饮酒的个体携带三个位点的突变等位基因可以降低HBV相关肝癌的发病风险(rs11776545,OR=0.61,95%CI=0.38-0.96;rs2275959,OR=0.60,95%CI=0.38-0.94;rs2275959,OR=0.63,95%CI=0.40-0.99)。5.以HBV自限清除组为对照,CHB/HCC组为病例,发现rs7221955和rs9891142与年龄有相乘的交互作用,且年龄大于60岁的个体携带rs7221955 C等位基因或rs9891142 C等位基因可以增加HBV慢性感染的风险(rs7221955,OR=1.82,95%CI=1.12-2.96;rs9891142,OR=1.78,95%CI=1.10-2.89)。结论:1.吸烟、饮酒及肿瘤家族史可以增加HBV慢性感染及HBV相关肝癌发病的风险。2.在年龄大于60岁的个体中,携带lnc-ACACA-1上的rs7221955 C或rs9891142C等位基因可以增加HBV慢性感染及HBV相关肝癌发病的风险,且携带CC单体型可以增加HBV相关肝癌发病的风险。3.在饮酒者中,携带lnc-RP11-150O12.3.1-1上的rs11776545 A、rs227595A及rs1008547 A等位基因可以降低HBV相关肝癌的发病风险。
[Abstract]:Objective: to analyze the single effect of lnc-ACACA-1 and lnc-RP11-150O12.3.1-1 genetic variation based on GWAS on the outcome of HBV infection and the interaction between gene and environment. Methods: Genome-wide association study was used in the study of Hepatitis B associated hepatocellular carcinoma (HCC). SNP(single nucleotide polymorphism was extracted from Hepatitis B associated hepatocellular carcinoma (HCC), and the study area was determined according to linkage disequilibrium between SNP. Seven SNPs from 2 lncRNA(lnc-ACACA-1 and lnc-RP11-150 O12.3.1-1) rs9891142rs11776545rs22759545rs2275959rs2275959rs2278320rs2298321rs10085477.554 patients with chronic hepatitis B patientsCHBand 644 patients with hepatitis B associated with hepatitis B were selected. A case-control study was conducted to analyze the effects of unit points and gene-environment interactions on the outcome of HBV infection by using a multi-classification logistic regression model combined with a multi-factor dimensionality reduction method. Results: 1. In the environmental factor analysis, smoking was used. Drinking, family history of cancer were all risk factors of chronic infection of HBV and HBV associated liver cancer (smoking) 7.67-95CI5.82-10.12; drinking or6.2495 + 0.19-0.32; family history of cancer: 4.63N95 CIQ 3.20-6.73.2.In the control group of HBV self-clearance group, the interaction between rs7221955 and rs9891142 was found to be multiplied and added with age. Moreover, carrying the rs7221955 C allele or rs9891142 C allele in individuals over 60 years old could increase the risk of chronic HBV infection. Rs722195 / 95 CIN 1.06-3.21 rs9891142 ORT 1.7895 CIN 1.03-3.100.3. the self-limiting HBV clearance group was used as a control group, and it was found that there was an additive effect between rs7221955 and age. Moreover, carrying the rs7221955 C allele or rs9891142 C allele in individuals over 60 years old could increase the risk of HBV associated liver cancer. Rs722195 / 95 ORT 1.82 / 95CI1.05-3.16 rs9891142 / 1. 04-3.100.At the same time, carrying CC haplotype could also increase the risk of HBV associated liver cancer, which was 1.02-1.70.4.The CHB group was used as a control group. It was found that the interaction between rs11776545nrs2275959 / rs1008547 and the family history of the tumor was multiplied and added, and the individuals who drank alcohol carried mutation alleles at three loci, which could reduce the risk of HBV related liver cancer, I. e., CI0.38-0.96rs2275959 / 95, CI0.38-0.94rs227595OR.0.38-0.94rs227595ORA 0.6395CI0.40-0.995.The HBV self-exfoliated group was used as a control group. It was found that rs7221955 and rs9891142 have multiplying effects on age, and that individuals over 60 years of age carry rs7221955 C allele or rs9891142 C allele, which can increase the risk of chronic infection of HBV. Rs722195 / 95CII 1.12-2.96 rs9891142 ORA 1.7895CI1.10-2.891.Conclusion: 1. Smoking, smoking, smoking. Drinking alcohol and cancer family history could increase the risk of HBV chronic infection and HBV associated liver cancer. In individuals over 60 years old, carrying rs7221955 C or rs9891142C allele on lnc-ACACA-1 could increase the risk of HBV chronic infection and HBV associated hepatocellular carcinoma. And carrying CC haplotype increased the risk of HBV associated HCC. Among drinkers, carrying rs11776545 Agnes 227595A and rs1008547 A alleles on lnc-RP11-150O12.3.1-1 decreased the risk of HBV associated HCC.
【学位授予单位】：广东药科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62

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