本文選題：多囊卵巢綜合征　切入點(diǎn)：ANRIL　出處：《安徽醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的本研究目的是探究ANRIL多態(tài)性與中國漢族人群多囊卵巢綜合征的易感性。 方法在中國漢族女性中收集139例多囊卵巢綜合征患者和141例對照者，提取DNA，設(shè)計探針引物通過實時熒光PCR TaqMan探針方法對INK4區(qū)域反義非編碼RNA(ANRIL)的一個SNPrs1333049進(jìn)行基因分型分析。 結(jié)果在PCOS患者中，各項生化指標(biāo)和臨床表現(xiàn)在各基因型之間差異無統(tǒng)計學(xué)意義。通過分析TaqMan探針基因分型的結(jié)果，rs1333049位可以分為3種基因型：CC，CG,GG。通過統(tǒng)計分析，PCOS患者和對照者間基因型分布和等位基因頻率差異無統(tǒng)計學(xué)意義(2=1.87, P=0.17;2=3.25, P=0.20)。 結(jié)論染色體9p21上rs1333049多態(tài)性與PCOS高雄激素血癥無關(guān)。 目的為探究CITED2基因在卵巢早衰的疾病發(fā)生過程中的作用，本研究將在卵巢早衰病人中篩查CITED2基因潛在的突變，以確認(rèn)CITED2基因與該疾病的關(guān)系。 方法收集189例特發(fā)性卵巢早衰患者和200例健康女性對照的外周血樣，提取DNA后，PCR擴(kuò)增直接測序探查CITED2基因啟動子區(qū)和編碼區(qū)的變異。隨后，構(gòu)建相應(yīng)質(zhì)粒，通過哺乳動物雙雜交,雙螢光素酶報告實驗,亞細(xì)胞定位等功能試驗檢驗CITED2基因中突變位點(diǎn)的作用。 結(jié)果對189例卵巢早衰患者和200例健康對照女性的CITED2基因編碼區(qū)和啟動子區(qū)測序峰圖，進(jìn)行chromas軟件解讀比對，一位POF患者的CITED2基因編碼區(qū)和啟動子區(qū)各發(fā)現(xiàn)一個突變，分別為c.634AG Met212Val和T-339G，這兩個突變均未在正常對照中發(fā)現(xiàn),且這兩個突變均不在研究熱點(diǎn)區(qū)域。通過體外功能實驗，，發(fā)現(xiàn)野生型CITED2可以通過調(diào)節(jié)HIF1-a來調(diào)控VEGF的表達(dá)。而實驗發(fā)現(xiàn)的編碼區(qū)突變在雙熒光實驗和哺乳動物雙雜交試驗中均可通過競爭性抑制HIF1-a與CBP/300結(jié)合，來恢復(fù)VEGF的表達(dá)。亞細(xì)胞定位可見野生型和突變型CITED2對于細(xì)胞定位并無明顯影響。啟動子中的突變相較于野生型可以升高基因的表達(dá)。 結(jié)論首次在中國漢族特發(fā)性POF患者中發(fā)現(xiàn)CITED2基因中的突變，并通過功能實驗進(jìn)一步明確了突變可能的作用，并由此推斷對于其可能與POF的發(fā)生相關(guān)。
[Abstract]:Objective to explore the relationship between ANRIL polymorphism and susceptibility to polycystic ovary syndrome (PCOS) in Chinese Han population. Methods A total of 139 polycystic ovary syndrome (PCOS) patients and 141 controls were collected from Han women in China, and a probe primer was designed to analyze a SNPrs1333049 of INK4 region antisense noncoding RNAs by real-time fluorescence PCR TaqMan probe method. Results in PCOS patients, There was no significant difference in biochemical indexes and clinical manifestations among genotypes. The results of TaqMan probe genotyping could be divided into three genotypes: 1: CCG GG. By statistical analysis of genotypes between PCOS patients and controls, the genotypes of rs1333049 could be divided into 3 genotypes. There was no significant difference in distribution and allele frequency (P = 1.87, P = 0.17, P = 0.20, P = 0.20). Conclusion rs1333049 polymorphism on chromosome 9p21 is not associated with PCOS hyperandrogenemia. Objective to investigate the role of CITED2 gene in the pathogenesis of premature ovarian failure (POF). In this study, potential mutations of CITED2 gene were screened in premature ovarian failure patients to confirm the relationship between CITED2 gene and the disease. Methods Peripheral blood samples of 189 patients with idiopathic premature ovarian failure and 200 healthy female controls were collected. After DNA was extracted, the mutation of promoter and coding region of CITED2 gene was detected by direct sequencing. Then the corresponding plasmids were constructed. The function of mutation site in CITED2 gene was tested by mammalian two-hybrid, double-luciferase report and subcellular localization. Results the CITED2 gene coding region and promoter region were sequenced from 189 preterm ovarian failure patients and 200 healthy women, and chromas software was used to analyze and compare. One mutation was found in the CITED2 gene coding region and one in the promoter region in one POF patient, and one mutation was found in the CITED2 gene coding region and promoter region in one POF patient. C. 634AG Met212Val and T-339G. these two mutations were not found in normal control, and neither of them was found in the hot research area. It was found that wild-type CITED2 could regulate the expression of VEGF by regulating HIF1-a, and the coding region mutation could be inhibited by competitive inhibition of HIF1-a binding to CBP/300 in both bifluorescence and mammalian two-hybrid experiments. Subcellular localization showed that wild type and mutant CITED2 had no significant effect on cellular localization. Mutations in promoter could increase gene expression compared with wild type. Conclusion the mutation of CITED2 gene was first found in Chinese Han patients with idiopathic POF, and the possible role of the mutation was further clarified by functional experiments, and it was deduced that the mutation might be related to the occurrence of POF.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R711.75

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