本文選題：HIV-1　切入點：ESNs人群　出處：《華中科技大學》2011年博士論文　論文類型：學位論文

【摘要】：研究目的 1.以中國漢族HIV-1暴露而血清陰性者(HIV-1-exposed seronegative subjects, ESNs人群)為研究對象,以健康對照人群和人類免疫缺陷病毒I型(Human Immunodeficiency Virus Type 1, HIV-1)攜帶者為對照,探討三組人群DC-SIGN和DC-SIGNR基因多態(tài)性與HIV-1不易感性的關(guān)系。 2.分析三組人群HIV-1感染相關(guān)受體的表達差異,從蛋白質(zhì)表達水平上尋找與HIV-1不易感性相關(guān)的受體。 3.從基因多態(tài)性的角度解釋與HIV-1不易感性密切相關(guān)的受體差異表達原因。 研究方法 應(yīng)用擴增片段長度多態(tài)性(PCR-ALFP)的方法進行DC-SIGN和DC-SIGNR基因多態(tài)性分析；應(yīng)用流式細胞術(shù)分析HIV-1感染相關(guān)受體的表達差異；應(yīng)用序列特異引物PCR (sequence-specific primers, PCR-SSP)分析HLA基因多態(tài)性；應(yīng)用SPSS13.0統(tǒng)計軟件分析三組人群之間受體表達和基因型分布的差異。 主要研究結(jié)果 1. DC-SIGN在三組人群中以7/7型為主,三組人群共檢出9個非7/7基因型,但DC-SIGN各基因型分布差異無統(tǒng)計學意義(P=0.648); DC-SIGNR具有高度多態(tài)性,7/5、5/5和6/7基因型的頻率從ESN人群、健康對照人群和HIV-1攜帶者逐漸降低,同時5和6等位基因的頻率也呈現(xiàn)均勻下降,但各基因型分布差異無統(tǒng)計學意義(P=0.782)； 2. ESNs人群T淋巴細胞HLA-DR+CD4和HLA-DR+CD8均顯著性低于健康對照人群(P=0.024,0.009),這兩項指標同時呈現(xiàn)顯著性正相關(guān)(P0.001,r=0.960)；利用HLA-DR+CD8的雙峰分布特征可以將健康對照人群分為高低表達兩群； 3.確切概率法卡方檢驗結(jié)果顯示,三個基因座的多態(tài)性位點中只有A*03和B*55在三組人群中的分布差異有顯著性。健康對照人群HLA基因型的分析發(fā)現(xiàn),A*02和A*24基因型在HLA-DR+CD8表達高低兩組的分布有顯著性差異(P=0.020,0.038)；等位基因分析也驗證了這個多態(tài)性變異分布的差異(P=0.007,0.009),DRB1*09等位基因分布也有顯著性差異(P=0.028)；A*02多態(tài)性變異與HLA-DR在CD8陽性細胞表面的表達有顯著性負相關(guān)(P=0.008)；A*24多態(tài)性變異與HLA-DR在CD8陽性細胞表而的表達有顯著性正相關(guān)(P=0.045)。 研究結(jié)論 1.我國漢族人群DC-SIGN基因多態(tài)性變異很低,沒有繼續(xù)研究的意義；DC-SIGNR基因多態(tài)性對于HIV-1不易感性的意義需要大樣本的驗證或細胞生物學實驗數(shù)據(jù)的支持； 2.對于中國漢族人群,T淋巴細胞低活化狀態(tài)與中國漢族人群HIV-1不易感性密切相關(guān),從統(tǒng)計學分析和生物學意義上可以將中國漢族人群按照HLA-DR+CD8活化高低分為HIV-1易感人群和不易感人群； 3. HLAA*02多態(tài)性變異可能是中國漢族人群HIV-1感染的保護性因素,而HLAA*24多態(tài)性變異可能是感染的危險因素。 創(chuàng)新性 1.首次在國內(nèi)ESNs人群的研究中設(shè)定了定量的的入選標準； 2.在國內(nèi)首次報道HLA-DR的高低表達與中國漢族人群HIV-1不易感性密切相關(guān)； 3.首次報道HLA-A*02多態(tài)性變異可能是中國漢族人群HIV-1感染的保護性因素,而HLA-A*24多態(tài)性變異可能是感染的危險因素。
[Abstract]:research objective
1. to Chinese Han HIV-1 exposed seronegative individuals (HIV-1-exposed seronegative subjects, ESNs group) as the research object, to a group of healthy people and human immunodeficiency virus type I (Human Immunodeficiency Virus Type 1, HIV-1) carriers as control, three groups of DC-SIGN and DC-SIGNR gene polymorphism and HIV-1 susceptibility.
2. the differences in the expression of HIV-1 related receptors in the three groups were analyzed, and the receptors associated with the HIV-1 non susceptibility were found from the protein expression level.
3. from the perspective of genetic polymorphisms, the reasons for the differential expression of the receptor, which is closely related to the HIV-1 susceptibility, are explained.
research method
Application of amplified fragment length polymorphism (PCR-ALFP) method for the analysis of DC-SIGN and DC-SIGNR gene polymorphism; analysis of differentially expressed HIV-1 infection related receptors by flow cytometry; using sequence specific primer PCR (sequence-specific primers PCR-SSP) analysis of HLA gene polymorphism; analysis of receptor expression and genotype differences between the three groups people using SPSS13.0 statistical software.
Main research results
1. DC-SIGN to 7/7 in the three groups, the three groups were detected in 9 non 7/7 genotype, but the genotype distribution of DC-SIGN showed no significant difference (P=0.648); DC-SIGNR has highly polymorphism, 7/5,5/5 and 6/7 genotypes from ESN group, healthy control group and HIV-1 carriers decreased gradually at the same time, the 5 and 6 allele frequencies showed uniform decline, but the genotype distribution difference was not statistically significant (P=0.782);
2. ESNs HLA-DR+CD4 and HLA-DR+CD8 T lymphocyte populations were significantly lower than those in healthy controls (P=0.024,0.009), these two indicators also showed significant positive correlation (P0.001, r=0.960); the Shuangfeng HLA-DR+CD8 distribution can be divided into healthy control group two group level expression;
3. exact test chi square test showed that there was significant difference in the distribution of only A*03 and B*55 in the three groups in the three polymorphic loci loci. Analysis of healthy control group HLA genotype, A*02 genotype distribution and A*24 level of the two groups had significant difference in the expression of HLA-DR+CD8 (P=0.020,0.038); allele analysis also verified the polymorphism distribution difference (P=0.007,0.009), DRB1*09 allele distribution had significant difference (P=0.028); A*02 polymorphism and HLA-DR has significant negative correlation in the expression of CD8 positive cell surface (P=0.008); A*24 polymorphism and HLA-DR in CD8 positive cells and expression have significant positive correlation (P=0.045).
research conclusion
1., the variation of DC-SIGN gene polymorphism in Chinese Han population is very low, which has no significance for further research. The significance of DC-SIGNR gene polymorphism for HIV-1 is not susceptible, which needs large sample validation or cell biology experimental data support.
2., for Chinese Han population, the low activation status of T lymphocytes is closely related to HIV-1's susceptibility to Chinese Han population. From statistical analysis and biological significance, Chinese Han population can be divided into HIV-1 susceptible group and non susceptible group according to HLA-DR+CD8 activation level.
3. HLAA*02 polymorphism may be a protective factor for HIV-1 infection in Chinese Han population, and HLAA*24 polymorphism may be a risk factor for infection.
Innovativeness
1. for the first time, a quantitative admission standard was set in the study of the domestic ESNs population.
2. the high and low expression of HLA-DR is closely related to the non susceptibility of HIV-1 in Chinese Han population for the first time in China.
3., for the first time, it is reported that HLA-A*02 polymorphism may be a protective factor of HIV-1 infection in Chinese Han population, while HLA-A*24 polymorphism may be a risk factor for infection.

【學位授予單位】：華中科技大學
【學位級別】：博士
【學位授予年份】：2011
【分類號】：R181.3

【引證文獻】

相關(guān)碩士學位論文 前1條

1 劉秀瑋;河南省漢族人群CISH、IFN-γ基因多態(tài)性與性暴露HIV易感性研究[D];鄭州大學;2012年

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本文編號：1641143