HIV感染合并肾脏病患者APOL1基因突变检测

发布时间：2018-01-21 05:26

本文关键词： 获得性免疫缺陷病毒肾脏病载脂蛋白L1 基因突变　出处：《遵义医学院》2017年硕士论文　论文类型：学位论文

【摘要】：目的:非洲裔黑人HIV感染伴肾损害患者中,载脂蛋白L1(apolipoprotein-L1,APOL1)基因变异(尤其是G1和G2)是重要的危险因素之一,但我们前期针对我国终末期肾病的研究没有发现这两种变异,是否存在APOL1的其他变异还不清楚。本研究针对我国HIV感染合并肾损害个体进行APOL1基因突变检测。方法:分析6例HIV感染合并肾脏病患者临床特点,并收集外周血DNA。检索确认APOL1基因序列,设计调控区、外显子的扩增引物,行聚合酶链反应(polymerase chain reaction,PCR)扩增,扩增产物经琼脂糖电泳验证,最后进行APOL1调控区、编码区基因测序,并与4名HIV感染非肾脏病患者、60名地域匹配正常对照、千人基因组测序结果,进行突变基因频率统计差异分析。结果:(1)6例患者均有不同程度血尿、蛋白尿、血白蛋白降低,2例患者血肌酐升高,2例患者有血脂紊乱,1例患者合并乙型肝炎病毒感染,1例患者合并丙型肝炎病毒感染。(2)外周血DNA测序结果显示1例患者携带APOL1基因DNA调控区A-565G杂合子突变;6例患者均携带APOL1基因DNA编码区G496A(Glu166Lys)、G732A(Met244Lle)和G812A(Arg271Lys)的错义突变,以及C702A、G1008A的同义突变。(3)与4名HIV感染非肾脏病患者、60名地域匹配正常对照、千人基因组测序相比,未发现新的突变,除部分突变基因频率与非洲裔个体有差异外,与HIV感染无肾脏病对照、正常对照以及其它亚裔个体无显著统计学差异。结论:本研究中,10例HIV感染患者,6例有肾脏损害,其中2例已经出现血肌酐升高,提示HIV感染肾脏损害较常见且预后不良。本研究未发现APOL1基因G1/G2突变,并且APOL1基因调控区、编码区未发现其他特殊变异,提示我国HIVAN发病可能存在其他危险因素。
[Abstract]:Objective: apolipoprotein-L1 (apolipoprotein-L1) was found in African-American patients with HIV infection and renal impairment. APOL1) gene mutation (especially G1 and G2) is one of the important risk factors, but our previous studies on end-stage nephropathy in China did not find these two variants. It is not clear whether there are other mutations in APOL1. In this study, APOL1 gene mutations were detected in individuals with HIV infection and renal damage in China. Methods:. The clinical features of 6 patients with HIV infection complicated with kidney disease were analyzed. The primer of APOL1 gene sequence, regulatory region and exon were obtained. PCR polymerase chain reaction- PCR was performed. The PCR products were confirmed by agarose electrophoresis. Finally, the APOL1 regulatory region was carried out. The coding region gene was sequenced, and the results of genome sequencing of thousands of people were matched with the normal control group of 4 patients with HIV infection and 60 patients with non-renal disease. Results there were 6 patients with different degree of hematuria, proteinuria and 2 patients with elevated serum creatinine and 2 patients with dyslipidemia. One patient was complicated with hepatitis B virus infection. DNA sequencing from peripheral blood of one patient with hepatitis C virus infection showed that one patient carried A-565G heterozygote mutation in the DNA regulatory region of APOL1 gene. All of the 6 patients were carrying G496A Glu166Lys. DNA coding region of APOL1 gene. The missense mutation and C702A of G732Agna Met244Lleand G812Agna Arg271Lys. The synonym mutation of G1008A was compared with that of 4 patients with HIV infection and 60 patients with non-renal disease. There was no new mutation found in the genome sequencing of thousands of people. There was no significant difference in the frequency of mutated genes with those of African Americans, with HIV infection without kidney disease, with normal controls and other Asian individuals. Conclusion: in this study. Renal damage was found in 6 of 10 patients with HIV infection, 2 of whom had elevated serum creatinine. In this study, no G1 / G2 mutation of APOL1 gene was found, and no other special mutations were found in the regulatory region and coding region of APOL1 gene. The results suggest that there may be other risk factors for the onset of HIVAN in China.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.91;R692

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