本文選題：子宮內(nèi)膜異位癥　切入點：血管內(nèi)皮生長因子受體　出處：《河北醫(yī)科大學》2014年碩士論文　論文類型：學位論文

【摘要】：目的：子宮內(nèi)膜異位癥（endometriosis，Ems，簡稱內(nèi)異癥）指具有活性的子宮內(nèi)膜腺體或間質成分在子宮內(nèi)膜及子宮肌層以外出現(xiàn)、生長、浸潤、反復出血、可形成結節(jié)及包塊，引起疼痛和不育。子宮內(nèi)膜異位癥是婦科常見疾病，在育齡期婦女其發(fā)病率達10%。研究表明：在內(nèi)異癥的發(fā)病過程中，內(nèi)異癥病灶中血管生成及血液供應起重要作用。新生血管形成是內(nèi)異癥病變形成中重要的環(huán)節(jié)，這一觀點基本被認可。血管內(nèi)皮生長因子（Vascular Endothelial Growth Factor，VEGF）是生理性及病理性血管生成最重要調(diào)節(jié)物，VEGF主要通過結合其酪氨酸激酶受體VEGFR-2發(fā)揮其促血管生成生物活性。本研究旨在探討VEGFR-2基因上的單核苷酸多態(tài)性（Single Nucleotide Polymorphisms，SNPs）位點與子宮內(nèi)膜異位癥發(fā)病風險的關系，其結果可能從基因水平進一步探討內(nèi)異癥的發(fā)病機制，并為其預防及診治提供重要理論依據(jù)。 方法：本實驗采用病例-對照研究，分析VEGFR-2基因上的遺傳變異與內(nèi)異癥發(fā)病風險的關系。研究對象包括571例內(nèi)異癥患者（病例組），580例健康對照個體（對照組）。采集研究對象的外周靜脈血5ml，采用蛋白酶K消化-飽和氯化鈉鹽析法提取外周血白細胞DNA。根據(jù)HapMap數(shù)據(jù)庫中VEGFR-2基因上的中國北方漢族人群的數(shù)據(jù)，利用Haploview軟件，通過htSNPs（haplotype tag Single Nucleotide Polymorphisms）的方法對VEGFR-2基因上的SNP位點進行篩選，最終確定了5個多態(tài)性位點：+1192C/T（rs2305948）、+1719T/A（rs1870377）、IVS6+54C/T（rs7692791）、IVS25-92G/A（rs1531289）和+31C/T（rs7667298）。采用聚合酶鏈反應和連接酶檢測反應（polymerase chain reaction-ligase detection reaction，PCR-LDR）技術，檢測病例組和對照組單核苷酸多態(tài)性位點的基因型和等位基因型頻率分布情況。數(shù)據(jù)統(tǒng)計分析采用SPSS13.0版軟件包（SPSSCompany，Chicago，Illinois，USA）進行分析，P0.05被認為差異有統(tǒng)計學意義。病例組和對照組的年齡差異采用t檢驗。對照組基因型頻率分布行χ2檢驗，進行Hardy-weinberg平衡分析。比較病例組和對照組各位點基因型和等位基因頻率分布采用χ2檢驗。以非條件Logistic回歸方法計算相對風險度的比值比（odds ratio，OR）及其95%可信區(qū)間（confidenceinterval，CI）。 結果： 1.內(nèi)異癥患者的年齡與其對照組相比，差異無統(tǒng)計學意義（P＞0.05）。統(tǒng)計學分析顯示對照組中VEGFR-2基因上的5個多態(tài)位點的基因型頻率分布均符合Hardy-weinberg平衡（P＞0.05）。 2. VEGFR-2基因+1192C/T多態(tài)的C和T等位基因頻率在對照組和內(nèi)異癥組分別為：86.0%，14.0%和89.3%，10.7%，兩組相比存在明顯差異（P=0.017）。與C/C基因型相比，C/T+T/T基因型的攜帶者內(nèi)異癥的發(fā)病風險明顯降低，OR值為0.75（95%CI=0.57-0.99）。 3. VEGFR-2基因+1719T/A多態(tài)的T/T，T/A，A/A三種基因型頻率在對照組和內(nèi)異癥組中分別為：30.2%，50.7%，19.1%和30.3%，49.0%，20.7%，差異無統(tǒng)計學意義（P=0.780）；T和A等位基因頻率分別為：55.5%，44.5%和54.8%，45.2%，兩組相比無差異（P=0.735）。 4. VEGFR-2基因+31C/T多態(tài)的C/C，C/T，T/T三種基因型頻率在對照組和內(nèi)異癥組中分別為：41.4%，47.6%，11.0%和42.2%，48.3%，9.5%，差異無統(tǒng)計學意義（P=0.677）；C和T等位基因頻率分別為：65.2%，34.8%和66.4%，33.6%，兩組相比無差異（P=0.543）。 5. VEGFR-2基因-92G/A多態(tài)的G/G，G/A，A/A三種基因型頻率在對照組和內(nèi)異癥組中分別為：62.6%，33.8%，3.6%和65.7%，31.0%，，3.3%，差異無統(tǒng)計學意義（P=0.551）；G和A等位基因頻率分別為：79.5%，20.5%和81.2%，18.8%，兩組相比無差異（P=0.308）。 6. VEGFR-2基因+54T/C多態(tài)的T/T，T/C，C/C三種基因型頻率在對照組和內(nèi)異癥組中分別為：34.7%，49.7%，15.7%和36.6%，46.4%，17.0%，差異無統(tǒng)計學意義（P=0.540）；T和C等位基因頻率分別為：59.5%，40.5%和59.8%，40.2%，兩組相比無差異（P=0.955）。 結論： VEGFR-2基因外顯子7區(qū)+1192C/T多態(tài)性位點可能與中國北方漢族婦女子宮內(nèi)膜異位癥的發(fā)病風險相關，與C/C基因型相比，C/T+T/T基因型的攜帶者子宮內(nèi)膜異位癥的發(fā)病風險明顯降低。VEGFR-2基因+1719T/A，+31C/T，-92G/A，+54C/T多態(tài)性位點可能與中國北方漢族婦女子宮內(nèi)膜異位癥的發(fā)病風險無關。
[Abstract]:Objective: Endometriosis (endometriosis, Ems, referred to as endometriosis) refers to endometrial glands with active or stromal elements in the endometrium and myometrium outside appearance, growth, invasion, repeated hemorrhage, can form nodules and mass, causing pain and infertility. Endometriosis is a common gynecological disease and in women of childbearing age and the incidence rate of 10%. research shows that: in the pathogenesis of endometriosis and endometriosis lesions in vascular formation and blood supply plays an important role. Neovascularization is an important link in endometriosis lesion formation, this point is recognized. Vascular endothelial growth factor (Vascular Endothelial Growth Factor. VEGF) is the physiological and pathological angiogenesis is the most important regulator of VEGF, mainly by binding to its receptor tyrosine kinase VEGFR-2 plays in promoting the activity of angiogenesis. The purpose of this study was to investigate the biological in VEGFR-2 The relationship between Single Nucleotide Polymorphisms (SNPs) loci and the risk of endometriosis may result from further investigation of the pathogenesis of endometriosis at gene level, and provide important theoretical basis for its prevention and treatment.
Methods: This study used a case-control study, the relationship between the genetic variation analysis of VEGFR-2 gene and the pathogenesis of endometriosis risk. The study included 571 cases of endometriosis patients (case group), 580 healthy individuals (control group). Collected peripheral venous blood 5ml, using proteinase K digestion saturated sodium chloride salting out extraction of peripheral white blood cells of DNA. according to the VEGFR-2 HapMap database on the gene China hanpopulation data, using Haploview software, through htSNPs (haplotype tag Single Nucleotide Polymorphisms) is the method of SNP VEGFR-2 alleles were identified 5 polymorphic loci: +1192C/T (rs2305948) +1719T/A, (rs1870377), IVS6+54C/T (rs7692791), IVS25-92G/A (rs1531289) and +31C/T (rs7667298). Using polymerase chain reaction and ligase detection reaction (polymerase chain reaction-liga Se detection reaction, PCR-LDR) detection technology, the case group and the control group of single nucleotide polymorphism genotype and allele frequency distribution. Using SPSS13.0 software package for statistical analysis of data (SPSSCompany, Chicago, Illinois, USA) analysis, P0.05 was considered statistically significant. The age difference between cases and controls group by t test. The control group genotype frequency distribution for 2 test, Hardy-weinberg analysis. The balance between case group and control group each genotype and allele frequency distribution of 2 test was used. With no conditional Logistic regression models were used to calculate oddsratios (odds ratio, OR) and 95% confidence interval (confidenceinterval, CI).
Result錛

本文編號：1623759