發(fā)布時間：2018-05-05 17:41

  本文選題：多系統(tǒng)萎縮 + COQ2基因��； 參考：《大連醫(yī)科大學(xué)》2016年碩士論文

【摘要】：研究背景與目的:多系統(tǒng)萎縮是一種進展性的神經(jīng)系統(tǒng)變性病,致殘、致死率較高,目前發(fā)病原因尚不明確,且無可延緩疾病進展的有效治療方法。近年來越來越多的研究表明多系統(tǒng)萎縮的發(fā)病存在遺傳相關(guān)性,日本的一項大樣本研究證明COQ2基因的變異V393A能夠增加多系統(tǒng)萎縮患病風(fēng)險。本實驗旨在分析散發(fā)性多系統(tǒng)萎縮患者的發(fā)病與COQ2基因變異的關(guān)系,探討亞洲人群多系統(tǒng)萎縮病變的病因及治療方法,提高對多系統(tǒng)萎縮病變的認(rèn)識。方法:實驗分為病例組和對照組,病例組為133例散發(fā)性多系統(tǒng)萎縮患者,對照組為200例非神經(jīng)系統(tǒng)變性病患者(包括51例周圍神經(jīng)病,25例中樞神經(jīng)系統(tǒng)感染性疾病,23例累及中樞的結(jié)締組織病,19例腦梗死,18例肌肉疾病,12例頸椎、腰椎椎關(guān)節(jié)強硬,8例神經(jīng)衰弱癥,7例癲癇,5例頭痛以及32例其他非神經(jīng)系統(tǒng)變性病)。實驗樣本為從上述患者的外周血中提取的DNA樣本。我們對病例組COQ2基因外顯子1、2、6、7進行聚合酶鏈?zhǔn)椒磻?yīng)擴增,提純相應(yīng)的擴增產(chǎn)物,然后對相應(yīng)外顯子進行測序并通過與正常人類COQ2基因序列的對比發(fā)現(xiàn)基因多態(tài)性核苷酸。運用限制性內(nèi)切酶片段長度多態(tài)性分析以及等位基因特異性聚合酶鏈?zhǔn)椒磻?yīng)對病例組中已發(fā)現(xiàn)的變異進行二次檢測以確保測序結(jié)果的準(zhǔn)確性,同時以此兩種方法檢測對照組中的基因變異。統(tǒng)計學(xué)分析方法運用四格表檢驗比較兩組間基因突變類型、例數(shù)與多系統(tǒng)萎縮的發(fā)病的相關(guān)性。結(jié)果:在病例組中發(fā)現(xiàn)基因變異G21S(c.61G-A)1例,L25V(c.73T-G)7例,P157S(c.469C-T)1例,V393A(c.1178T-C)7例,X422K(c.1264T-A)1例。對照組中發(fā)現(xiàn)基因變異G21S(c.61G-A)1例,L25V(c.73T-G)4例,P157S(c.469C-T)0例,V393A(c.1178T-C)11例,X422K(c.1264T-A)0例。病例組中所有變異經(jīng)限制性內(nèi)切酶片段長度多態(tài)性分析以及等位基因特異性聚合酶鏈?zhǔn)椒磻?yīng)證實是確定存在的。Tsuji S等人曾報道變異V393A為多發(fā)于亞洲人種中的基因變異,并且是散發(fā)多系統(tǒng)萎縮C型的發(fā)病危險因素,可引起線粒內(nèi)輔酶Q10的合成減少。Sharma M,Jeon BS和Chen YP等人曾報道變異V393A在歐洲、韓國和中國人群的病例對照研究中與多系統(tǒng)萎縮的發(fā)病不相關(guān)。在我們的實驗中,變異V393A在實驗組和對照組中無明顯差異,不能證明與多系統(tǒng)萎縮的發(fā)病相關(guān)。Tsuji S等人曾報道在日本散發(fā)多系統(tǒng)萎縮患者中發(fā)現(xiàn)變異P157S 1例,在我們的病例組中也發(fā)現(xiàn)1例,對照組中0例,統(tǒng)計學(xué)無明顯差異。G21S、L25V、X422K是從未被報道過的變異。G21S和X422K在病例組和對照組中無統(tǒng)計學(xué)差異,不能證明與多系統(tǒng)萎縮的發(fā)病相關(guān)。L25V在病例組和對照組中無統(tǒng)計學(xué)差異,而在病例組OPCA患者與對照組中有統(tǒng)計學(xué)差異(p=0.04)。結(jié)論:定位于COQ2基因上的變異L25V是一個在日本人群中新發(fā)現(xiàn)的橄欖腦橋小腦萎縮的遺傳易感因素,而之前報道過的變異V393A不能增加多系統(tǒng)萎縮的患病風(fēng)險。
[Abstract]:Background & AIM: Multi-system atrophy is a progressive neurodegenerative venereal disease with high mortality. At present, the cause of the disease is not clear, and there is no effective treatment to delay the progress of the disease. In recent years, more and more studies have shown that there is a genetic correlation in the pathogenesis of multi-system atrophy. A large sample study in Japan has shown that the mutation of COQ2 gene V393A can increase the risk of multi-system atrophy. The purpose of this study was to analyze the relationship between the pathogenesis of sporadic multisystem atrophy and the variation of COQ2 gene, to explore the etiology and treatment of multisystem atrophy in Asian population, and to improve the understanding of multisystem atrophy. Methods: the experiment was divided into two groups: the case group was 133 patients with sporadic multi-system atrophy. The control group consisted of 200 patients with non-neurotic diseases (including 51 peripheral neuropathy 25 central nervous system infectious diseases 23 central nervous system connective tissue diseases 19 cerebral infarction 18 muscle diseases 12 cervical vertebrae). There were 8 cases of neurasthenia in lumbar vertebrae and 7 cases of epilepsy, 5 cases of headache and 32 cases of other non-neurotic diseases. The experimental samples were DNA samples extracted from the peripheral blood of the patients mentioned above. We amplified the exon 1 of COQ2 gene by polymerase chain reaction and purified the corresponding product. Then we sequenced the corresponding exon and found the polymorphic nucleotides by comparing with the normal human COQ2 gene sequence. Restriction endonuclease fragment length polymorphism (RFLP) and allele-specific polymerase chain reaction (allele-specific polymerase chain reaction) were used to re-detect the mutations found in the case group in order to ensure the accuracy of the sequencing results. At the same time, two methods were used to detect the gene variation in the control group. Statistical analysis method was used to compare the relationship between the type of gene mutation, the number of cases and the incidence of multiple system atrophy between the two groups. Results: in the case group, there were 7 cases of G21S(c.61G-A)1 gene mutation, 7 cases of P157S, c. 469C-TU, 1 case of V393An, c. 1178T-C, 7 cases of X422KN c. 1264T-An, 1 case of P157S, c. 469C-TU, 7 cases of X422KU c. 1264T-An. In the control group, there were 4 cases of G21S(c.61G-A)1 with gene mutation (P157SU, c.469C-TU) and 0 cases of V393Anc. 1178T-C (n = 11) with X422KU c. 1264T-An (n = 0). The results were as follows: (1) in the control group, there were 4 cases of P157SX c. 469C-TU. All mutations in the case group were confirmed by restriction endonuclease fragment length polymorphism analysis and allele-specific polymerase chain reaction. Tsuji S et al reported that the mutation V393A was a gene mutation in Asian species. It is also a risk factor for sporadic multisystem atrophy type C, which may cause a decrease in the synthesis of coenzyme Q10. Sharma M Jeon BS and Chen YP have reported that variant V393A is present in Europe. Case-control studies in Korean and Chinese populations were not associated with multiple-system atrophy. In our experiment, there was no significant difference between the experimental group and the control group. Tsuji S et al reported that one case of variant P157S was found in patients with sporadic multisystem atrophy in Japan. In our case group, one case was also found, and there was no significant difference between control group and control group. There was no significant difference between the two groups. There was no statistical difference between the case group and the control group, and there was no statistical difference between the case group and the control group. There was no significant difference in the incidence of multisystem atrophy. L25V was not significantly different between the case group and the control group, but there was a significant difference between the case group and the control group in the OPCA patients and the control group. Conclusion: the mutation L25V located on the COQ2 gene is a new genetic susceptibility factor for olivary pontine cerebellar atrophy in Japanese population, while the previously reported mutation V393A does not increase the risk of multiple system atrophy.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R741

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 Saft C.;Andrich J.;Mü ller T. ;M. Stü cker;劉安;;多系統(tǒng)萎縮中部分排汗功能紊亂(德國)[J];世界核心醫(yī)學(xué)期刊文摘(皮膚病學(xué)分冊);2005年12期

2 劉瑞春,時寶林,李鳳玲;多系統(tǒng)萎縮4例[J];臨床薈萃;2005年07期

3 夏程;郎森陽;;“十字征”和多系統(tǒng)萎縮1例報告[J];中國神經(jīng)精神疾病雜志;2006年01期

4 Rohde S;Glatz K;H釨hnel S;張菁;;多系統(tǒng)萎縮[J];放射學(xué)實踐;2006年05期

5 Soma H;Yabe I;Takei A.;蔡同建;;多系統(tǒng)萎縮的遺傳學(xué)研究[J];世界核心醫(yī)學(xué)期刊文摘(神經(jīng)病學(xué)分冊);2006年05期

6 莊柏翔;;多系統(tǒng)萎縮基礎(chǔ)及臨床研究[J];中國醫(yī)師進修雜志;2006年22期

7 孫正偉;金鋒;牛力;白小紅;王立華;賈薇;孫琳;;多系統(tǒng)萎縮5例臨床分析[J];中國實用神經(jīng)疾病雜志;2006年05期

8 張玉生;徐仁O5;廖杰芳;吳裕臣;萬慧;黃經(jīng)緯;洪道俊;王進華;李莉;;多系統(tǒng)萎縮“十字征”16例報道及文獻(xiàn)復(fù)習(xí)[J];臨床薈萃;2007年05期

9 魏金香;;1例多系統(tǒng)萎縮誤診病例分析[J];首都醫(yī)藥;2008年14期

10 郭詠娣;王平;;多系統(tǒng)萎縮1例[J];中國現(xiàn)代醫(yī)生;2009年28期

相關(guān)會議論文 前10條

1 顧衛(wèi)紅;王國相;楊斯柳;王康;段曉慧;;統(tǒng)一多系統(tǒng)萎縮評估量表與多系統(tǒng)萎縮病程的相關(guān)性分析[A];第十一屆全國神經(jīng)病學(xué)學(xué)術(shù)會議論文匯編[C];2008年

2 王家鳳;胡興越;;多系統(tǒng)萎縮患者肛門括約肌肌電圖的特點分析[A];2009年浙江省神經(jīng)病學(xué)學(xué)術(shù)年會論文匯編[C];2009年

3 張波;鮑遠(yuǎn)程;楊文明;童建兵;方向;;多系統(tǒng)萎縮的中西醫(yī)診療[A];2005全國中醫(yī)腦病學(xué)術(shù)研討會論文匯編[C];2005年

4 刁建萍;何志義;;39例多系統(tǒng)萎縮臨床特點及進展預(yù)后分析[A];中華醫(yī)學(xué)會第十三次全國神經(jīng)病學(xué)學(xué)術(shù)會議論文匯編[C];2010年

5 郝紅琳;劉秀琴;黃顏;王含;孫鶴陽;;多系統(tǒng)萎縮的睡眠多導(dǎo)圖分析[A];中華醫(yī)學(xué)會第十三次全國神經(jīng)病學(xué)學(xué)術(shù)會議論文匯編[C];2010年

6 戚曉昆;劉鵬;李麗萍;錢海蓉;姜樹軍;段楓;王巍;;多系統(tǒng)萎縮臨床特點分析及肛門肌電圖對其診斷價值的評價[A];中華醫(yī)學(xué)會第七次全國神經(jīng)病學(xué)學(xué)術(shù)會議論文匯編[C];2004年

7 李麗萍;錢海蓉;戚曉昆;;肛門括約肌肌電圖對多系統(tǒng)萎縮的診斷價值[A];中華醫(yī)學(xué)會第七次全國神經(jīng)病學(xué)學(xué)術(shù)會議論文匯編[C];2004年

8 劉建軍;熊葶;;多系統(tǒng)萎縮的不尋常表現(xiàn)一例[A];中華醫(yī)學(xué)會第七次全國神經(jīng)病學(xué)學(xué)術(shù)會議論文匯編[C];2004年

9 丁美萍;宣夏清;毛善英;;“十字征”和多系統(tǒng)萎縮[A];中華醫(yī)學(xué)會第七次全國神經(jīng)病學(xué)學(xué)術(shù)會議論文匯編[C];2004年

10 李輝華;徐文苑;周美鴻;萬慧;吳裕臣;;多系統(tǒng)萎縮的早期診斷與治療(附26例臨床分析)[A];江西省中西醫(yī)結(jié)合學(xué)會第二次神經(jīng)科學(xué)術(shù)交流會論文匯編[C];2005年

相關(guān)重要報紙文章 前2條

1 海軍總醫(yī)院神經(jīng)內(nèi)科教授 戚曉昆邋李麗萍;懷疑多系統(tǒng)萎縮 查查肛門肌電圖[N];健康報;2008年

2 羅火山;神秘怪病何以代代相傳[N];大眾衛(wèi)生報;2007年

相關(guān)博士學(xué)位論文 前2條

1 宋春俠;多系統(tǒng)萎縮中醫(yī)證候的初步研究[D];北京中醫(yī)藥大學(xué);2008年

2 楊海O，

本文編號：1848675