【作者】 杨菲；

【导师】 樊晓光；

【作者基本信息】 山西医科大学 ， 医学免疫学， 2006， 硕士

【摘要】 目的:为了了解HLA-A、B、DR位点的基因多态性与原发性肾病综合征的联系关系,寻找原发性肾病综合征的HLA的易感基因及山西省部分原发性肾病综合征患者出现的基因频率的变化规律,研究原发性肾病综合征患者的病因及致病机理,我们选取了山西汉族30例原发性肾病综合征患者及45例汉族健康人的DNA进行了研究。材料和方法:实验组:选2005年山西医科大学第一附属医院肾内科临床表现为激素抵抗型肾病综合征的患者30例。其中:22例成人病例中,经肾脏活组织穿刺检查,有10例IgAN(IgA肾病),5例MsPGN(系膜增生性肾小球肾炎),4例MPGN(膜增殖型肾小球肾炎),3例MN(膜性肾病)。30例病例均排除了可能的继发性肾病综合征,作为实验组。对照组:选取45例志愿者,身体健康,无肾病综合征者。23例患者标本及45例对照组标本采用聚合酶链反应序列特异性引物(PCR-SSP)方法,7例标本采用聚合酶链反应序列特异性探针(PCR-SSO)方法,检测了30例激素抵抗型肾病综合征(SRNS)患者和45例正常健康者的HLA-A、B、DR基因型别,研究了SRNS的基因频率与正常对照者的基因频率的关系。30例标本中,分别比较了全部30例SRNS与正常对照者基因频率的关系,22例成人SRNS与正常对照者基因频率的关系、8例儿童SRNS与正常对照者基因频率的关系,10例活检为IgAN的SRNS与正常对照者基因频率的关系。结果:SRNS患者组中,用23种引物,共检出12种HLA-A等位基因,基因频率范围为1.67%～31.67%。其中HLA-A*02、*24、*11等位基因的频率较高(31.67%、16.67%、15.00%),HLA-A*01、*29、*30、*32等位基因的频率较低(均为1.67%)。用47种引物,共检出17种HLA-B等位基因,基因频率范围为1.67%～23.33%。其中HLA-B*15、*44等位基因的频率较高(23.33%、20.00%),HLA-B*07、*08、*37、*38、*53等位基因的频率较低(均为1.67%)。用23种引物,共检出12种HLA-DRB1等位基因,基因频率范围为1.67%～21.67%。其中HLA-DRB1*04、*07、*09等位基因的频率较高(21.67%、16.67%、16.67%),HLA-DRB1*01、*13等位基因的频率较低(均为1.67%)。对照组中,用23种引物,共检出11种HLA-A等位基因,基因频率范围为1.11%～22.22%。其中HLA-A*02、*11、*03等位基因的频率较高(22.22%、15.56%、14.44%),HLA-A*23、*26、*33等位基因的频率较低(1.11%、2.22%、3.33%)。用47种引物,共检出22种HLA-B等位基因,基因频率范围为1.11%～12.22%。其中HLA-B*40、*13、*15等位基因的频率较高(12.22%、11.11%、11.11%),HLA-B*18、*37、*38、*39、*41、*45、*48、*55、*57等位基因的频率较低(均为1.11%)。用23种引物,共检出11种HLA-DRB1等位基因,基因频率范围为3.33%～17.78%。其中HLA-DRB1*15、*04等位基因的频率较高(17.78%、15.56%),HLA-DRB1*14等位基因的频率较低(3.33%)。SRNS组HLA-B*15、B*44与正常对照相比有显著性差异,其基因频率均高于对照组:更多还原

【Abstract】 Objectives: We choosed 30 patients with idiopathic nephrotic syndromes(INS)of Han Population of people in Shanxi and 45 healthy people in order to access the association of HLA-A、B、DR gene polymorphism with,to look for susceptible HLA genes to INS’s patients and the HLA gene frequency in INS’s patients, and to investigate the etiopathogenisis and pathogenesis of INS.Materials and Methods : 30 patients were selected ,those who were with steroid-resistant nephrotic syndrome (SRNS) from department of nephrology of the first affliated hospital of Shanxi Medical University in 2005. Out of 30 patients, 22 are adults and 8 are children and renal biopsy was performed in 22 adults patients, 10 of whom showed IgA nephropathy (IgAN), 5 of whom showed mesangial proliferative glomerulonephritis (MsPGN), 4 of whom showed membrane proliferative glomerulonephritis (MPGN), 3 of whom showed membranous nephropathy (MN). whereas 45 healthy people without Nephrotic Syndrome are in the control group.The alleles of HLA-A、B、DR loci in 23 patients and in 45 healthy ones in control group were subtyped by polymorase chain reaction with sequence specific primer (PCR-SSP) and the alleles of HLA-A、B、DR loci in 7 patients were subtyped by polymorase chain reaction with sequence specific oligonucleotide probe (PCR-SSO). Results are analyzed between HLA-A、B、DR allelic frequency of SRNS and those gene frequencies of healthy control.HLA-A、B、DR allelic frequencies are analyzed in 30 SRNS patients, 22 adults patients, 8 children patients and 10 IgAN patients and in 45 healthy controls one by one.Results In SRNS group there were firstly 12 HLA-A alleles were observed by 23 specific primers and the range of allelic frequencies is from 1.67% to 31.67%. Among of them the HLA-A*02、*24、*11 allele are popular in the patients-----the frequency of them is 31.67%、16.67%、15.00% respectively , and the HLA-A*01、*29、*30、*32 are rare in the patients---the frequency of them is 1.67%. Secondly 17 HLA-B alleles were observed by 47 specific primers and the range of allelic frequencies is from 1.67% to 23.33%. Among of them the HLA-B*15、*44 allele are popular in the patients ---the frequency of them is 23.33%、20.00% respectively, and the HLA-B*07、*08、*37、*38、*53 are rare in the patients– all the frequency of them is 1.67%. Furthermore 12 HLA-DRB1 alleles were observed by 23 specific primers and the range of allelic frequencies is from 1.67% to 21.67%. Among of them the HLA-DRB1*04、07、09 allele are popular in the patients---the frequency of them is 21.67%、16.67%、16.67%更多还原