本文選題：慢性乙型肝炎病毒 + 感染��； 參考：《昆明醫(yī)科大學(xué)》2017年碩士論文

【摘要】：[目的]以慢性HBV感染人群、H]BV自限性感染人群和健康人群為研究對(duì)象,獲取其線粒體DNA控制區(qū)的遺傳變異和單倍型類群信息;明確研究組間線粒體DNA變異位點(diǎn)和單倍型類群的分布情況,分析不同人群變異位點(diǎn)和單倍型類群的差異。結(jié)合臨床數(shù)據(jù),探討候選線粒體DNA突變和單倍型類群與HBV易感性和感染結(jié)局的相關(guān)性。[方法]我們首先測(cè)定了來(lái)自云南省第二人民醫(yī)院肝病內(nèi)科和體檢中心的234例HBV自限性感染人群的外周血的線粒體DNA控制區(qū)序列,整合本課題組前期獲得的272例慢性HBV感染人群和312例健康人群線粒體DNA控制區(qū)序列進(jìn)行分析。將所獲得的數(shù)據(jù)和修訂后的劍橋參考序列(revised Cambridge Refrence Sequence;rCRs)進(jìn)行比對(duì),我們記錄了所有個(gè)體線粒體DNA控制區(qū)的種系突變信息。根據(jù)突變信息,我們參考已發(fā)表的世界人群線粒體DNA系統(tǒng)關(guān)系發(fā)育樹(shù),將研究對(duì)象的線粒體DNA數(shù)據(jù)劃分到特定的單倍型類群中。通過(guò)X2檢驗(yàn),我們對(duì)慢性HBV感染人群、HBV自限性感染人群和健康人群線粒體DNA控制區(qū)突變和單倍型類群的分布頻率進(jìn)行統(tǒng)計(jì)分析。結(jié)合臨床相關(guān)信息,對(duì)線粒體DNA單倍型類群的分布頻率與臨床特征的相關(guān)性進(jìn)行了分析。[結(jié)果]1線粒體DNA控制區(qū)研究結(jié)果:通過(guò)對(duì)來(lái)自云南省第二人民醫(yī)院肝病內(nèi)科和體檢中心的272例慢性HBV感染者、234例HBV自限性感染者和312例健康對(duì)照者外周血線粒體DNA測(cè)序,獲得818份線粒體DNA控制區(qū)全長(zhǎng)1124bp測(cè)序序列,慢性HBV感染組共計(jì)280個(gè)多態(tài)性位點(diǎn),HBV自限性感染組共計(jì)272個(gè)多態(tài)性位點(diǎn),健康對(duì)照組共計(jì)297個(gè)多態(tài)性位點(diǎn);其中慢性HBV感染組與健康對(duì)照組重疊多態(tài)性位點(diǎn)共計(jì)194個(gè),慢性HBV感染組特異位點(diǎn)85個(gè);慢性HBV感染組與HBV自限性感染組重疊多態(tài)性位點(diǎn)共計(jì)230個(gè),慢性HBV感染組特異性位點(diǎn)50個(gè);HBV自限性感染組和健康對(duì)照組重疊多態(tài)性位點(diǎn)共計(jì)168個(gè),HBV自限性感染組特異性位點(diǎn)104個(gè)。通過(guò)對(duì)818條序列進(jìn)行了單倍型類群的劃分,其中700條序列(慢性HBV感染人群231例,HBV自限性感染人群207例,健康人群262例)劃分入14種單倍型類群,分別為M*、M7、M8、C、D、D4、D5、A、R9、F、F1、B、B4、B5。未歸入以上14種單倍型類群者共118例(慢性HBV感染人群41例;HBV自限性感染人群27例;健康人群50例)。結(jié)合前人的數(shù)據(jù)進(jìn)行主成分分析,結(jié)果顯示我們研究的慢性HBV感染人群、HBV自限性感染人群和健康人群來(lái)源一致。2對(duì)mtDNA控制區(qū)突變位點(diǎn)進(jìn)行X2檢驗(yàn),慢性HBV感染人群和健康人群突變位點(diǎn)分布的分析顯示慢性HBV感染人群攜帶m.151CT的突變頻率(2.12%)顯著低于健康人群(7.37%);慢性HBV感染人群和HBV自限性感染人群的突變位點(diǎn)分布分析顯示慢性HBV感染人群攜帶m.146TC、m.310CT、m.310+C、m.523-524AC/del 的突變頻率(15.81%,20.22%,70.22%,41.18%)顯著高于HBV自限性感染人群(8.54%,11.54%,53.85%,25.64%),慢性HBV感染人群攜帶m.315+C、m.16274CT突變頻率(5.88%,3.30%)顯著低于HBV自限性感染人群(26.92%,7.26%);對(duì)HBeAg陽(yáng)性和HBeAg陰性慢性HBV感染人群的突變位點(diǎn)進(jìn)行分析顯示HBeAg陽(yáng)性人群攜帶m.16266CT的突變頻率(9.68%)明顯高于HBeAg陰性人群(2.38%)。3 mtDNA單倍群類型分布頻率分析,結(jié)果顯示慢性HBV感染人群攜帶單倍群類型D5的分布頻率(8.09%)明顯高于健康人群(3.20%);慢性HBV感染人群攜帶單倍群類型D5的分布頻率(8.09%)明顯高于HBV自限性感染人群(3.84%);健康人與HBV自限性感染者、HBeAg陽(yáng)性與HBeAg陰性慢性HBV感染者中單倍型類群分布無(wú)差異。4對(duì)攜帶mtDNA單倍型類群D5和非攜帶單倍型類群D5的慢性HBV感染人群、HBV自限性感染人群、健康人群、HBeAg陽(yáng)性和HBeAg陰性慢性HBV感染人群進(jìn)行一般臨床特征分析,結(jié)果顯示三組研究對(duì)象性別、年齡和肝功能指標(biāo)無(wú)差異;5從性別層面上對(duì)男女分別進(jìn)行單倍型類群分布頻率的比對(duì),發(fā)現(xiàn)各組間單倍型類群分布無(wú)差異。[結(jié)論]1線粒體DNA多態(tài)性位點(diǎn)m.151CT在健康人群中的頻率顯著高于慢性HBV感染者,提示該位點(diǎn)變異可能是慢性HBV感染的潛在保護(hù)因素,即未攜帶該突變的健康人群可能對(duì)HBV易感;2 多態(tài)性位點(diǎn) m.146TC、m.310CT、m.310+C、m.523-524AC/del 在慢性 HBV感染人群中的頻率明顯高于HBV自限性感染人群,提示該變異位點(diǎn)可能是HBV持續(xù)感染的潛在危險(xiǎn)因素;慢性HBV感染者攜帶m.315+C、m.16247CT突變頻率顯著低于HBV自限性感染者,提示該變異位點(diǎn)可能與HBV清除相關(guān);3多態(tài)性位點(diǎn)m.16266CT在HBeAg陽(yáng)性人群的突變頻率明顯高于HBeAg陰性人群,提示m.16266CT變異可能與HBV慢性感染結(jié)局不同相關(guān)。4 mtDNA單倍型類群D5可能是HBV持續(xù)感染的危險(xiǎn)因素,且與性別、年齡肝功能無(wú)關(guān)。
[Abstract]:[Objective] to study the genetic variation and the haplotype group information of the mitochondrial DNA control area with chronic HBV infected people and H]BV self limiting infection population and healthy population, and to clarify the distribution of the mitochondrial DNA mutation and haplotype groups in the study group, and analyze the differences in the variation and haplotype groups of different populations. The correlation of the candidate mitochondrial DNA mutation and the haplotype group to the susceptibility to HBV and the infection outcome. [Methods] we first measured the mitochondrial DNA control region of the peripheral blood from 234 cases of HBV self limited infection from the second people's Hospital of Yunnan province. The sequence of the mitochondrial DNA control region of 272 chronic HBV infected people and 312 healthy people was analyzed. The data obtained were compared with the revised Cambridge reference sequence (revised Cambridge Refrence Sequence; rCRs). We recorded the mutation information of the mitochondrial DNA control area of all individuals. The mitochondrial DNA system of the world population was published, and the mitochondrial DNA data of the subjects were divided into a specific haplotype group. Through X2 test, we analyzed the distribution frequency of the mitochondrial DNA control region and the haplotype groups in the chronic HBV infected population, the HBV self limiting infection population and the healthy population. Combined with clinical information, the correlation between the distribution frequency of mitochondrial DNA haplotype groups and clinical characteristics was analyzed. [results]1 mitochondrial DNA control area study results: 272 cases of chronic HBV infection, 234 cases of HBV self limiting infection and 312 healthy pairs of HBV from the liver disease internal medicine and physical examination center of the second people's Hospital of Yunnan province. In the peripheral blood mitochondrial DNA sequencing, 818 mitochondrial DNA control region full length 1124bp sequencing sequences, 280 polymorphic loci in the chronic HBV infection group, 272 polymorphic loci in the HBV self limiting infection group, and 297 polymorphic loci in the healthy control group, of which the chronic HBV infection group and the healthy control group were polymorphic loci in total. 194, 85 special sites in chronic HBV infection group, 230 overlapped polymorphic loci in chronic HBV infection group and HBV self limiting infection group, 50 specific loci in chronic HBV infection group, 168 polymorphic loci in HBV self limiting infection group and healthy control group, 104 specific loci in the self limited infection group. 818 sequence entered into 818 sequences. 700 sequences (231 cases of chronic HBV infection, 207 cases of HBV self limiting infection, 262 healthy people) were divided into 14 haplotypes, including M*, M7, M8, C, D, D4, D5, A, R9, 118 cases (41 cases of chronic infection). 27 people and 50 healthy people. Combined with previous data, principal component analysis showed that we studied chronic HBV infected people, HBV self limiting infection population and healthy population origin consistent.2 to X2 test of mutation site in mtDNA control area. Analysis of chronic HBV infection and distribution of mutation sites in healthy population showed chronic HBV The mutation frequency (2.12%) of the infected people (2.12%) was significantly lower than that of the healthy population (7.37%), and the distribution analysis of the mutation sites in the chronic HBV infected people and the HBV self limited infection population showed that the frequency of mutation frequency of m.146TC, m.310CT, m.310+C, m.523-524AC/del (15.81%, 20.22%, 70.22%, 41.18%) of chronic HBV infected people (15.81%, 20.22%, 70.22%, 41.18%) was significantly higher than that of the HBV self limiting sex Infected people (8.54%, 11.54%, 53.85%, 25.64%), chronic HBV infected people carrying m.315+C, m.16274CT mutation frequency (5.88%, 3.30%) significantly lower than the HBV self limited infection population (26.92%, 7.26%); HBeAg positive and HBeAg negative chronic HBV infected population of the mutation site analysis showed that HBeAg positive people carry the mutation frequency of m.16266CT (9.68%) Ming (9.68%) The frequency analysis of the single group type distribution of.3 mtDNA was significantly higher than that of HBeAg negative group (2.38%). The results showed that the frequency of the distribution of unhaploid group D5 in chronic HBV infected people (8.09%) was significantly higher than that of the healthy population (3.20%), and the frequency of the distribution of unhaploid group D5 in chronic HBV infected people (8.09%) was significantly higher than that of the HBV self restricted population (3.84%). There was no difference in the distribution of haplotype groups in patients with HBV self limiting infection, HBeAg positive and HBeAg negative chronic HBV infection,.4 for chronic HBV infected people carrying mtDNA haplotype group D5 and non haplotype group D5, HBV self limiting infection population, healthy population, HBeAg positive and HBeAg negative chronic infection population. The results showed that there was no difference in sex, age and liver function between the three groups. 5 the distribution frequencies of haplotype groups were compared between men and women at the gender level, and there was no difference in the distribution of haplotype groups in each group. [conclusion]1 mitochondrial DNA polymorphism site m.151CT was significantly higher in healthy people than in chronic HBV sense. The mutant may be a potential protective factor for chronic HBV infection, that is, healthy people who do not carry the mutation may be susceptible to HBV, and 2 polymorphic loci, m.146TC, m.310CT, m.310+C, and m.523-524AC/del are significantly higher in chronic HBV infected people than in HBV self limiting infections, suggesting that the heterotopic point may be a HBV holding. The potential risk factors for continued infection; chronic HBV infected people carrying m.315+C, the mutation frequency of m.16247CT was significantly lower than that of HBV self limiting infection, suggesting that the heterotopic point may be associated with HBV clearance; 3 the mutation frequency of m.16266CT in HBeAg positive population is significantly higher than that of HBeAg negative population, suggesting that m.16266CT variation may be associated with HBV chronic infection. .4 mtDNA haplotype D5 may be a risk factor for persistent HBV infection and is not associated with gender, age and liver function.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.62

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本文編號(hào)：2107170