雌激素及雌激素受体α基因多态性与高危人群HCV感染转归的关系

发布时间：2018-03-01 02:27

本文关键词： 有偿献血雌二醇 HCV感染肝功能丙型肝炎病毒雌激素受体α 基因多态性自限清除持续感染　出处：《南京医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：第一部分有偿献血人群血浆雌二醇与HCV感染及肝功能情况关系的研究 [背景]20世纪80年代末至90年代初,江苏省镇江市部分地区存在非法的、不规范的商业性血液采集,造成了丙型肝炎等经血传播的传染病在有偿献血人群中的感染和扩散。这部分人群大多有单采血浆史和采全血史,且多为家庭妇女,大多从未接受丙型肝炎病毒(hepatitis C virus, HCV)检测和相应的治疗干预。 [目的]分析有偿献血人群血浆雌二醇(Estradiol, E2)水平与丙型肝炎病毒感染情况及肝功能指标的关系,为HCV感染转归的致病机理及其预防提供参考依据。 [方法]以江苏省某县级市于1990年前后曾发生有偿献血行为的男性和大于50岁以上的女性为研究对象,共收集样本195例,其中健康对照组56例,自限清除组44例和持续感染组95例。通过检测三组人群的E2和肝功能指标包括丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、总胆红素(total bilirubin, Tbil)、直接胆红素(direct bilirubin, Dbil)、谷酰转肽酶(gamma-glutamyl transpeptidase, GGT)、碱性磷酸酶(alkaline phosphatase, ALP)的浓度,分析它们与HCV感染转归及相互之间的关系。 [结果]以献全血次数、单采血浆次数和脂肪肝和／或肝硬化为协变量,三组间的ALT(P=0.003)和AST(P=0.025)水平差异存在统计学意义；E2与ALT、AST、GGT和ALP呈弱的负相关,但都不具有统计学意义,P值均0.05。多因素Logistic回归分析结果显示,年龄增长是慢性HCV感染者血清ALT升高的独立危险因素(OR=1.122,95%CI=1.036-1.215)。 [结论]为预防HCV感染的发生,应加强并规范采供血的管理,而连续的大样本的随访研究有助于进一步探讨血浆雌二醇水平对HCV感染转归及肝功能的影响作用。第二部分中国高危人群雌激素受体α基因多态性与HCV感染转归关系的研究 [背景]丙型肝炎病毒感染所引起的丙型肝炎是一种呈世界性分布的传染病,据估计目前全世界约有1.8亿HCV感染者,严重威胁人类健康并呈增长趋势,我国一般人群HCV感染率为3.2%。不同个体HCV感染的预后不同,除与病毒本身因素相关外,宿主某些基因的多态性,可能导致机体免疫功能状态的差异,因而决定着HCV感染的转归。 [目的]探讨中国高危人群中雌激素受体a (estrogen receptor a, ERa)基因多态性与丙型病毒肝炎感染转归的关系,以便于为今后丙型肝炎的个体化防治提供科学依据。 [方法]运用Taqman技术检测429例HCV自限感染者,880例HCV持续感染者和1174例健康对照者的ERα中rs2077647, rs9340799, rs2234693, rs1801132, rs9322354, rs2228480和rs3798577位点的基因多态性,并分析这七个位点基因型分布与HCV易感性和感染后转归的关系。 [结果]在调整年龄、性别、感染途径和HCV基因分型后,Logistic回归分析显示rs2234693基因多态性与HCV感染有关(显性模型：调整OR=1.377,95%CI=1.126-1.778),进一步分层分析显示,C等位基因使青年组(≤55岁)和血液透析人群HCV感染的风险增加(P均0.007)。另外有三个位点的相加模型在分层分析(rs2077647在男性中,rs9340799在有偿献血人群中,rs1801132在青年组中)也发现与HCV的感染有关(P均0.007)。rs2228480中的A等位基因使HCV感染者进展为持续感染者的风险增加(显性模型：调整OR=1.203,95%CI=1.154-1.552),分层分析显示,在女性及有偿献血人群中仍会使该风险增加(P均0.007)。基因-环境的交互作用分析中,rs2228480与性别在HCV感染结局中存在交互作用(P=2.13×10-3)。单倍型分析(rs2077647, rs9340799和rs2234693)表明,CAC单倍型在青年组(P=3.24×10-3)及男性(P=5.51×10-4)中能增加HCV感染的风险,而CAT单倍型在降低女性('=2.27×10-4)HCV感染的风险。 [结论]以上均表明rs2077647, rs9340799, rs2234693, rs1801132和rs2228480五个位点的基因多态性在不同高危人群中与HCV的感染转归可能有一定的关联,但需要进一步扩大样本量和开展功能性研究来对本次实验结果进行验证。
[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.

【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.63

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