人类免疫缺陷病毒感染合并肾脏病载脂蛋白L1基因突变检测  

Detection of APOL1 gene mutation in HIV infection complicated with kidney disease

作　　者：张尧[1] 张正秀[2] 何洪斌[2] 刘婷婷[2] 李贵森[1] 王莉[1] ZHANG Yao ZHANG Zheng-xiu HE Hong-bin LIU Ting-ting LI Gui-sen WANG Li(Department of Nephrology ＆ Nephrology Institute ,Sichuan Academy of Medical Sciences ＆ Sichuan Provincial People＇s Hospital, Chengdu 610072, China Department of Nephrology ,Panzhihua City Central Hospital ,Panzhihua 617067, China)

机构地区：[1]四川省医学科学院.四川省人民医院肾脏内科暨肾脏病研究所,四川成都610072 [2]四川省攀枝花市中心医院肾内科,四川攀枝花617067

出　　处：《实用医院临床杂志》2017年第2期25-28,共4页Practical Journal of Clinical Medicine

摘　　要：目的检测我国人类免疫缺陷病毒(HIV)感染合并或未合并肾损害个体进行载脂蛋白L1(apolipoprotein-L1,APOL1)基因突变。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,进行APOL1调控区、编码区基因测序,与4例HIV感染非肾脏病患者、60例地域匹配正常对照、千人基因组测序,进行突变基因频率比较。结果 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例患者合并乙肝感染,1例患者合并丙肝感染。全血DNA测序显示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)、C702A(同义突变)、G732A(Met244Lle)、G812A(Arg271Lys)、G1008A(同义突变)突变。与4例HIV感染非肾脏病患者、60例地域匹配正常对照、千人基因组测序相比,未发现新的突变,且突变基因频率分布差异无统计学意义。结论未发现非洲裔美国人HIV相关肾病常见的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HIV相关肾病可能存在其他危险因素。Objective To detect the mutation of apolipoprotein-L1 （APOL1） in HIV patients complicated with kidney disease. Methods We analyzed the clinical characteristics of six HIV patients complicated with kidtley disease. Then,we collected peripheral blood cell DNA and performed sequence analysis of the regulatory and coding regions in APOL1 gene. Finally, we compared the frequencies of the mutant alleles of the six patients with four HIV-infected patients without kidney disease and 60 matched normal con- trois as well as 1000 genomes project data. Results All the six cases presented different degrees of microscopic hematuria, proteinuria, serum albumin reduction. There were two patients with increased serum creatinine level, two with dyslipidemia, one with concomitant hepatitis B virus infection and one with concomitant hepatitis C virus infection. The whole blood DNA sequence analysis showed that there was a patient with a heterozygous mutation in the regulatory region （A-565G）. Five mutations in coding region at G496A （Glu166Lys） ,C702A （ synonymous mutation）, G732A （ Met244Lle）, GS12A （ Arg271Lys）, and G1008A （ synonymous mutation） were found in all the six cases. Compared to the four HIV-infected patients without kidney disease, 60 matched normal controls, and 1000 genomes project data,the frequencies of these variants were not statistically different. Conclusion No APOL1 G1/G2 mutations that were common in African Americans with HIV infection complicated with kidney disease are found in this study. There is also no other special variation of APOL1 gene in these patients. It may suggest that there could be other risk factors for the disease in our country.

关 键 词：HIV感染 肾脏病 载脂蛋白L1 基因突变 

分 类 号：R692[医药卫生—泌尿科学] R512.91[医药卫生—外科学]