本文選題：HBV相關(guān)肝癌　切入點(diǎn)：lncRNA　出處：《廣東藥科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:分析基于GWAS的lnc-ACACA-1和lnc-RP11-150O12.3.1-1遺傳變異對HBV感染結(jié)局影響的單獨(dú)作用及基因-環(huán)境交互作用。方法:基于乙肝相關(guān)肝癌的全基因組關(guān)聯(lián)研究(genome-wide association study,GWAS)文獻(xiàn),提取與乙肝相關(guān)肝癌有顯著關(guān)聯(lián)的SNP(single nucleotide polymorphism),根據(jù)SNP間的連鎖不平衡確定研究區(qū)域,在這些區(qū)域查找有潛在功能的lncRNA SNP,最終篩選出2個lncRNA(lnc-ACACA-1和lnc-RP11-150O12.3.1-1)上的7個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例乙肝相關(guān)肝癌患者(hepatocellular carcinoma,HCC)為研究對象,采用病例對照研究,應(yīng)用多分類logistic回歸模型與多因子降維法相結(jié)合的策略,系統(tǒng)分析單位點(diǎn)、基因-環(huán)境交互作用對HBV感染結(jié)局的影響。結(jié)果:1.在環(huán)境因素分析中,吸煙、飲酒、腫瘤家族史均是HBV慢性感染及HBV相關(guān)肝癌發(fā)病的危險因素(吸煙,OR=7.67,95%CI=5.82-10.12;飲酒,OR=6.24,95%CI=0.19-0.32;腫瘤家族史,OR=4.63,95%CI=3.20-6.73)。2.以HBV自限清除組為對照,CHB組為病例,發(fā)現(xiàn)rs7221955和rs9891142與年齡有相乘和相加的交互作用,且年齡大于60歲的個體攜帶rs7221955 C等位基因或rs9891142 C等位基因可以增加HBV慢性感染的風(fēng)險(rs7221955,OR=1.84,95%CI=1.06-3.21;rs9891142,OR=1.78,95%CI=1.03-3.10)。3.以HBV自限清除組為對照,HCC組為病例,發(fā)現(xiàn)rs7221955與年齡有相加的交互作用,且年齡大于60歲的個體攜帶rs7221955 C等位基因或rs9891142 C等位基因可以增加HBV相關(guān)肝癌的發(fā)病風(fēng)險(rs7221955,OR=1.82,95%CI=1.05-3.16;rs9891142,OR=1.80,95%CI=1.04-3.10),同時攜帶CC單體型也可增加HBV相關(guān)肝癌的發(fā)病風(fēng)險(OR=1.32,95%CI=1.02-1.70)。4.以CHB組為對照,HCC組為病例,發(fā)現(xiàn)rs11776545、rs2275959、rs1008547與腫瘤家族史有相乘和相加的交互作用,且有飲酒的個體攜帶三個位點(diǎn)的突變等位基因可以降低HBV相關(guān)肝癌的發(fā)病風(fēng)險(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自限清除組為對照,CHB/HCC組為病例,發(fā)現(xiàn)rs7221955和rs9891142與年齡有相乘的交互作用,且年齡大于60歲的個體攜帶rs7221955 C等位基因或rs9891142 C等位基因可以增加HBV慢性感染的風(fēng)險(rs7221955,OR=1.82,95%CI=1.12-2.96;rs9891142,OR=1.78,95%CI=1.10-2.89)。結(jié)論:1.吸煙、飲酒及腫瘤家族史可以增加HBV慢性感染及HBV相關(guān)肝癌發(fā)病的風(fēng)險。2.在年齡大于60歲的個體中,攜帶lnc-ACACA-1上的rs7221955 C或rs9891142C等位基因可以增加HBV慢性感染及HBV相關(guān)肝癌發(fā)病的風(fēng)險,且攜帶CC單體型可以增加HBV相關(guān)肝癌發(fā)病的風(fēng)險。3.在飲酒者中,攜帶lnc-RP11-150O12.3.1-1上的rs11776545 A、rs227595A及rs1008547 A等位基因可以降低HBV相關(guān)肝癌的發(fā)病風(fēng)險。
[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.
【學(xué)位授予單位】：廣東藥科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R512.62

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