本文選題：缺氧誘導(dǎo)因子 + 基因多態(tài)性��； 參考：《廣西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：缺氧誘導(dǎo)因子（Hypoxia inducible factor-1，HIF-1）作為缺氧環(huán)境下誘導(dǎo)的主要的核轉(zhuǎn)錄激活因子，在機(jī)體應(yīng)對(duì)缺氧的過(guò)程中發(fā)揮了重要作用。本實(shí)驗(yàn)主要通過(guò)對(duì)HIF-1α基因rs11549465和rs11549467兩個(gè)位點(diǎn)基因多態(tài)性的研究，探討在廣西地區(qū)人群中HIF-1α的基因型在HBV相關(guān)性肝炎、肝硬化、肝癌人群中的分布，以及HIF-1α的基因多態(tài)性與HBV相關(guān)性肝炎、肝硬化、肝癌的遺傳易感性的關(guān)系。 方法：篩選首次入院的HBV相關(guān)性肝臟疾病患者共442例作為病例組，其中包括153例慢性乙型肝炎患者（CHB組），132例乙型肝炎肝硬化患者（LC組），157例HBV相關(guān)性肝癌患者（HCC組），同時(shí)選取健康體檢者173例作為對(duì)照組。應(yīng)用聚合酶鏈反應(yīng)-限制性片段長(zhǎng)度多態(tài)性（PCR-RFLP）技術(shù)分別檢測(cè)HIF-1α基因rs11549465、rs11549467兩個(gè)位點(diǎn)的基因多態(tài)性，并利用DNA直接測(cè)序法驗(yàn)證與PCR-RFLP法檢測(cè)結(jié)果的吻合度，計(jì)算其基因型和等位基因頻率。采用擬和優(yōu)度χ2檢驗(yàn)對(duì)兩個(gè)SNP位點(diǎn)進(jìn)行哈-溫平衡檢測(cè)，并運(yùn)用logistic回歸分析校正性別、年齡等混雜因素，計(jì)算OR和95%CI，進(jìn)而分析兩個(gè)SNP位點(diǎn)基因多態(tài)性和HBV相關(guān)性肝炎、肝硬化、肝癌遺傳易感性的關(guān)系。運(yùn)用SHEsis軟件分別對(duì)HIF-1α基因兩個(gè)SNP位點(diǎn)進(jìn)行單倍型分析。 結(jié)果： 1.對(duì)照組與CHB組、LC組、HCC組各組的性別構(gòu)成比較差異無(wú)統(tǒng)計(jì)學(xué)意義（P0.05），然而各組在年齡構(gòu)成比較時(shí)發(fā)現(xiàn)，對(duì)照組與LC組和HCC組年齡比較差異均有統(tǒng)計(jì)學(xué)意義（P 0.05），同時(shí)CHB組與LC組和HCC組年齡比較差異亦有統(tǒng)計(jì)學(xué)意義（P0.05），其余的兩兩比較則差異均無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。HIF-1αrs11549465和rs11549467兩個(gè)SNP位點(diǎn)中，除rs11549465位點(diǎn)中的肝癌組（P0.05）外，其余組的基因型分布頻率均符合哈-溫平衡定律（P0.05）。 2. HIF-1αrs11549465位點(diǎn)發(fā)現(xiàn)CC、CT和TT三種基因型。將野生型CC基因型和等位基因C分別作為參照，通過(guò)logistic回歸分析校正年齡和性別混雜因素后發(fā)現(xiàn)，CT基因型在CHB與HCC組比較中差異有統(tǒng)計(jì)學(xué)意義（P0.05），，其余組包括等位基因組比較差異均無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。此外在男性人群亦發(fā)現(xiàn)同樣的結(jié)果。說(shuō)明CHB可能與HCC患病有相關(guān)性。 3. HIF-1αrs11549467位點(diǎn)發(fā)現(xiàn)GG、GA和AA三種基因型。將野生型GG基因型和等位基因G分別作為參照，通過(guò)logistic回歸分析校正年齡和性別混雜因素后發(fā)現(xiàn)，GA基因型和AA基因型與各組比較差異均無(wú)統(tǒng)計(jì)學(xué)意義，與等位基因A相比差異亦無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。 4.對(duì)性別進(jìn)行分層分析后發(fā)現(xiàn)HIF-1α中rs11549465和rs11549467兩個(gè)位點(diǎn)無(wú)論是在廣西男性人群中，還是在廣西女性人群中，其基因型和等位基因與CHB、LC以及HCC患病風(fēng)險(xiǎn)均未發(fā)現(xiàn)相關(guān)性。 5.將上述兩個(gè)SNP位點(diǎn)進(jìn)行單倍型構(gòu)建，結(jié)果發(fā)現(xiàn)在對(duì)照組與HCC組構(gòu)建的CA、CG單倍型中差異有統(tǒng)計(jì)學(xué)意義（P=0.025，OR=0.416；P=0.008，OR=2.327），在CHB組與HCC組構(gòu)建的CG、TG單倍型中差異亦有統(tǒng)計(jì)學(xué)意義（P=0.007，OR=2.408；P=0.020，OR=0.315） 結(jié)論： 1. HIF-1rs11549465位點(diǎn)的CT基因型可能降低CHB發(fā)展為HCC的發(fā)病風(fēng)險(xiǎn)。而rs11549467位點(diǎn)的多態(tài)性與HBV相關(guān)性肝炎、肝硬化、肝癌的患病風(fēng)險(xiǎn)無(wú)關(guān)。 2. rs11549465和rs11549467兩個(gè)位點(diǎn)構(gòu)建的單倍型分析中發(fā)現(xiàn)CA單倍型可能降低HCC的患病風(fēng)險(xiǎn)，而CG單倍型可能增加HCC的患病風(fēng)險(xiǎn)。CG單倍型亦可增加由CHB發(fā)展為HCC的患病風(fēng)險(xiǎn)，而TG單倍型則可降低CHB發(fā)展為HCC的患病風(fēng)險(xiǎn)。
[Abstract]:Objective: Hypoxia inducible factor-1 (HIF-1), as a major nuclear activator in anoxic environment, plays an important role in the process of coping with hypoxia. This experiment is mainly based on the study of the two gene polymorphisms of the HIF-1 alpha gene rs11549465 and rs11549467, and the study of people in Guangxi region. The genotype of HIF-1 alpha in the group is distributed in HBV related hepatitis, cirrhosis, liver cancer, and the genetic polymorphisms of HIF-1 A and the genetic susceptibility to HBV related hepatitis, cirrhosis, and liver cancer.
Methods: 442 cases of HBV related liver disease were selected for the first time, including 153 patients with chronic hepatitis B (group CHB), 132 cases of hepatitis B cirrhosis (group LC), 157 patients with HBV related liver cancer (group HCC), and 173 healthy persons as the control group. The polymerase chain reaction restriction was used. The fragment length polymorphism (PCR-RFLP) technique was used to detect the gene polymorphism of the two loci of the HIF-1 alpha gene rs11549465 and rs11549467, and the DNA direct sequencing was used to verify the anastomosis with the results of the PCR-RFLP assay, and to calculate the genotype and allele frequency of the allele. Two SNP loci were detected by the pseudo sum chi 2 test. The logistic regression analysis was used to correct the sex, age and other confounding factors, calculate OR and 95%CI, and then analyze the relationship between the genetic polymorphisms of two SNP loci and the genetic susceptibility to hepatitis, cirrhosis and liver cancer associated with HBV. Using the SHEsis software, the haplotype analysis of the two SNP loci of the HIF-1 a gene was performed respectively.
Result錛

本文編號(hào)：1825811