本文關(guān)鍵詞： 有償獻(xiàn)血 雌二醇 HCV感染 肝功能 丙型肝炎病毒 雌激素受體α 基因多態(tài)性 自限清除 持續(xù)感染　出處：《南京醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：第一部分 有償獻(xiàn)血人群血漿雌二醇與HCV感染及肝功能情況關(guān)系的研究 [背景]20世紀(jì)80年代末至90年代初,江蘇省鎮(zhèn)江市部分地區(qū)存在非法的、不規(guī)范的商業(yè)性血液采集,造成了丙型肝炎等經(jīng)血傳播的傳染病在有償獻(xiàn)血人群中的感染和擴(kuò)散。這部分人群大多有單采血漿史和采全血史,且多為家庭婦女,大多從未接受丙型肝炎病毒(hepatitis C virus, HCV)檢測(cè)和相應(yīng)的治療干預(yù)。 [目的]分析有償獻(xiàn)血人群血漿雌二醇(Estradiol, E2)水平與丙型肝炎病毒感染情況及肝功能指標(biāo)的關(guān)系,為HCV感染轉(zhuǎn)歸的致病機(jī)理及其預(yù)防提供參考依據(jù)。 [方法]以江蘇省某縣級(jí)市于1990年前后曾發(fā)生有償獻(xiàn)血行為的男性和大于50歲以上的女性為研究對(duì)象,共收集樣本195例,其中健康對(duì)照組56例,自限清除組44例和持續(xù)感染組95例。通過(guò)檢測(cè)三組人群的E2和肝功能指標(biāo)包括丙氨酸氨基轉(zhuǎn)移酶(alanine aminotransferase, ALT)、天冬氨酸氨基轉(zhuǎn)移酶(aspartate aminotransferase, AST)、總膽紅素(total bilirubin, Tbil)、直接膽紅素(direct bilirubin, Dbil)、谷酰轉(zhuǎn)肽酶(gamma-glutamyl transpeptidase, GGT)、堿性磷酸酶(alkaline phosphatase, ALP)的濃度,分析它們與HCV感染轉(zhuǎn)歸及相互之間的關(guān)系。 [結(jié)果]以獻(xiàn)全血次數(shù)、單采血漿次數(shù)和脂肪肝和／或肝硬化為協(xié)變量,三組間的ALT(P=0.003)和AST(P=0.025)水平差異存在統(tǒng)計(jì)學(xué)意義；E2與ALT、AST、GGT和ALP呈弱的負(fù)相關(guān),但都不具有統(tǒng)計(jì)學(xué)意義,P值均0.05。多因素Logistic回歸分析結(jié)果顯示,年齡增長(zhǎng)是慢性HCV感染者血清ALT升高的獨(dú)立危險(xiǎn)因素(OR=1.122,95%CI=1.036-1.215)。 [結(jié)論]為預(yù)防HCV感染的發(fā)生,應(yīng)加強(qiáng)并規(guī)范采供血的管理,而連續(xù)的大樣本的隨訪研究有助于進(jìn)一步探討血漿雌二醇水平對(duì)HCV感染轉(zhuǎn)歸及肝功能的影響作用。 第二部分 中國(guó)高危人群雌激素受體α基因多態(tài)性與HCV感染轉(zhuǎn)歸關(guān)系的研究 [背景]丙型肝炎病毒感染所引起的丙型肝炎是一種呈世界性分布的傳染病,據(jù)估計(jì)目前全世界約有1.8億HCV感染者,嚴(yán)重威脅人類健康并呈增長(zhǎng)趨勢(shì),我國(guó)一般人群HCV感染率為3.2%。不同個(gè)體HCV感染的預(yù)后不同,除與病毒本身因素相關(guān)外,宿主某些基因的多態(tài)性,可能導(dǎo)致機(jī)體免疫功能狀態(tài)的差異,因而決定著HCV感染的轉(zhuǎn)歸。 [目的]探討中國(guó)高危人群中雌激素受體a (estrogen receptor a, ERa)基因多態(tài)性與丙型病毒肝炎感染轉(zhuǎn)歸的關(guān)系,以便于為今后丙型肝炎的個(gè)體化防治提供科學(xué)依據(jù)。 [方法]運(yùn)用Taqman技術(shù)檢測(cè)429例HCV自限感染者,880例HCV持續(xù)感染者和1174例健康對(duì)照者的ERα中rs2077647, rs9340799, rs2234693, rs1801132, rs9322354, rs2228480和rs3798577位點(diǎn)的基因多態(tài)性,并分析這七個(gè)位點(diǎn)基因型分布與HCV易感性和感染后轉(zhuǎn)歸的關(guān)系。 [結(jié)果]在調(diào)整年齡、性別、感染途徑和HCV基因分型后,Logistic回歸分析顯示rs2234693基因多態(tài)性與HCV感染有關(guān)(顯性模型：調(diào)整OR=1.377,95%CI=1.126-1.778),進(jìn)一步分層分析顯示,C等位基因使青年組(≤55歲)和血液透析人群HCV感染的風(fēng)險(xiǎn)增加(P均0.007)。另外有三個(gè)位點(diǎn)的相加模型在分層分析(rs2077647在男性中,rs9340799在有償獻(xiàn)血人群中,rs1801132在青年組中)也發(fā)現(xiàn)與HCV的感染有關(guān)(P均0.007)。rs2228480中的A等位基因使HCV感染者進(jìn)展為持續(xù)感染者的風(fēng)險(xiǎn)增加(顯性模型：調(diào)整OR=1.203,95%CI=1.154-1.552),分層分析顯示,在女性及有償獻(xiàn)血人群中仍會(huì)使該風(fēng)險(xiǎn)增加(P均0.007)�；�-環(huán)境的交互作用分析中,rs2228480與性別在HCV感染結(jié)局中存在交互作用(P=2.13×10-3)。單倍型分析(rs2077647, rs9340799和rs2234693)表明,CAC單倍型在青年組(P=3.24×10-3)及男性(P=5.51×10-4)中能增加HCV感染的風(fēng)險(xiǎn),而CAT單倍型在降低女性('=2.27×10-4)HCV感染的風(fēng)險(xiǎn)。 [結(jié)論]以上均表明rs2077647, rs9340799, rs2234693, rs1801132和rs2228480五個(gè)位點(diǎn)的基因多態(tài)性在不同高危人群中與HCV的感染轉(zhuǎn)歸可能有一定的關(guān)聯(lián),但需要進(jìn)一步擴(kuò)大樣本量和開(kāi)展功能性研究來(lái)對(duì)本次實(shí)驗(yàn)結(jié)果進(jìn)行驗(yàn)證。
[Abstract]:Part one
Study on the relationship between plasma estradiol and HCV infection and liver function in the paid blood donors
[background]20 century at the end of 80s to early 90s, there are some areas of Jiangsu province Zhenjiang City illegal, commercial blood collection is not standardized, resulting in blood transmission of hepatitis C infection in blood donors in the infection and spread. Most of this part of the crowd with plasmapheresis and the history of mining history and blood. As a housewife, most have never received the hepatitis C virus (hepatitis C, virus, HCV) detection and corresponding intervention.
[Objective] to analyze the relationship between plasma Estradiol (E2) level and hepatitis C virus infection and liver function indexes in blood donors, so as to provide a reference for the pathogenesis and prevention of HCV infection.
[Methods] to a county-level city in Jiangsu in 1990 and had paid blood donation behavior of male and aged 50 or older women as the research object, collected 195 samples, including 56 cases of healthy controls, self limiting clearance group and 44 cases of persistent infection group 95 cases. Including alanine aminotransferase detected by three groups of E2 and liver function index (alanine aminotransferase, ALT), aspartate aminotransferase (aspartate, aminotransferase, AST), total bilirubin (total, bilirubin, Tbil), direct bilirubin (direct, bilirubin, Dbil), GGT (gamma-glutamyl transpeptidase, GGT), alkaline phosphatase (alkaline phosphatase. ALP) concentrations, analyze them with HCV infection outcome and the relationship between each other.
[results] to offer the number of blood, blood plasma and the number of fatty liver and / or cirrhosis as covariates, ALT between the three groups (P=0.003) and AST (P=0.025) were significant differences in the level of E2 and ALT, AST; and a weak negative correlation of GGT and ALP, but not with statistical significance. P values were 0.05. Logistic multivariate regression analysis showed that age was the independent risk of elevated serum ALT in patients with chronic HCV infection (OR=1.122,95%CI=1.036-1.215).
[Conclusion] in order to prevent the occurrence of HCV infection, we should strengthen and standardize the management of blood collection and administration. Continuous large sample follow-up study is helpful to further explore the effect of plasma estradiol level on HCV infection outcome and liver function.
The second part
A study on the relationship between the polymorphism of estrogen receptor alpha gene and the outcome of HCV infection in Chinese high risk population
[background] hepatitis C virus infection caused by hepatitis C is an infectious disease worldwide, it is estimated that about 180 million of the world HCV infection, a serious threat to human health and increase the general population in China, HCV infection rate for the prognosis of 3.2%. HCV infection in different individuals, in addition to related factors with the virus itself, host polymorphisms of some genes may lead to differences in immune function, which determines the outcome of HCV infection.
[Objective] to explore the relationship between a estrogen receptor A (ERa) gene polymorphism and the prognosis of hepatitis C virus infection in Chinese high-risk population, so as to provide a scientific basis for individualized prevention and treatment of hepatitis C in the future.
[method] using Taqman technology to detect 429 cases of HCV self limiting infection, rs2077647, 880 cases of HCV infection and 1174 healthy controls ER alpha rs9340799, rs2234693, rs1801132, rs9322354, rs2228480 gene polymorphism and rs3798577 loci, and analyze the relationship between the seven genotype distribution and susceptibility to HCV and the outcome of infection.
[results] after adjustment for age, gender, type of infection pathway and HCV gene, Logistic regression analysis showed that rs2234693 gene polymorphism and HCV infection (dominant model: OR=1.377,95%CI=1.126-1.778 adjustment), further stratified analysis showed that the C allele of the young group (< 55 years) and hemodialysis group increased the risk of HCV infection (P 0.007). Another analysis of additive model in three loci stratification (rs2077647 in males, rs9340799 in blood donors, rs1801132 in the youth group) also found with HCV infection (P 0.007).Rs2228480 risk A allele of the HCV infection in persistent infection the increase (dominant model: OR=1.203,95%CI=1.154-1.552 adjustment), stratified analysis showed that in women and paid blood donors will still make the increased risk (P 0.007). Analysis of gene environment interaction, and rs2228480 In the presence of gender interaction in the outcome of HCV infection (P=2.13 * 10-3). Haplotype analysis (rs2077647, rs9340799 and rs2234693) showed that CAC haplotype in young group (P=3.24 * 10-3) and male (P=5.51 * 10-4) can increase the risk of HCV infection, and CAT haplotypes in the lower women's risk of HCV ('=2.27 * 10-4) infection.
[Conclusion] above showed that rs2077647, rs9340799, rs2234693, rs1801132 and rs2228480 five gene polymorphism loci in different high-risk population with HCV infection outcome may have some relevance, but the need to further expand the sample size and carry out functional studies to validate the results of the experiment.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R512.63

【參考文獻(xiàn)】

相關(guān)期刊論文 前5條

1 石素勝,劉秀云,何祖根;肝癌組織雌激素受體表達(dá)與生物學(xué)特征的研究[J];癌癥;2000年06期

2 王雷永;毛羽;郁正亞;郎振為;夏峰;沈冰;;人肝細(xì)胞癌中雌激素受體及其亞型的表達(dá)與臨床意義[J];腹部外科;2007年06期

3 郜玉峰;魏少峰;張亞飛;葉s，

本文編號(hào)：1550017