特发性局灶节段性肾小球硬化患者SYNPO基因变异和多态性分析  

Variances and SNPs of SYNPO gene in idiopathic focal segmental glomerulosclerosis

作　　者：陈楠[1] 戴胜川[1] 王朝晖[1] 潘晓霞[1] 王伟铭[1] 张文[1] 任红[1] 陈晓农[1] 冯旗[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院肾脏科,上海200025 [2]中国科学院上海生命科学院国家基因中心

出　　处：《肾脏病与透析肾移植杂志》2008年第4期325-330,368,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：上海市卫生局重点学科基金(05III001);上海市重点学科基金(T0201);上海市领军人才基金;上海市科委重点项目(07JC14037);上海市青年科技启明星培养计划(03QD14021)

摘　　要：目的:探讨特发性局灶节段性肾小球硬化(idiopathic FSGS)中SYNPO基因变异和多态(SNP)特点。方法:以82例特发性FSGS和70例健康人为研究对象。盐析法提取外周血基因组DNA、引物设计、PCR扩增后测序。基因数据库匹配筛选,结合患者肾组织Synaptopodin和患者父母头发DNA检测验证其致病意义。SNP位点H-W平衡检验后行基因频率、基因型和临床表型关联分析。结果:1例5′UTR变异1-24G>A,其父母未发现相同变异,肾组织Synaptopodin较正常和非变异NSFSGS组下降(321.33±18.01比514.00±31.21,P<0.01);1例单核苷酸变异437C>T(Pro146Leu),肾组织Synaptopodin较正常和非变异非NSFSGS组下降(385.67±15.95比635.50±23.95,P<0.01);1例单核苷酸变异1903A>C(Thr635Pro),其父母未发现相同变异,肾组织Synaptopodin较正常和非变异NSFSGS组明显下降(160.67±27.68比514.00±31.21,P<0.01);另外发现1例新同义变异1488C>T(Thr496Thr)和5例同义变异1578C>T(Pro526Pro)。未发现疾病易感SNP位点。结论:散发性FSGS患者中可能存在SYNPO基因致病变异位点,其可能在散发性FSGS发病中起作用。Objective：To study the variances and single nucleotide polymorphisms （SNPs） of gene SYNPO in idi- opathic focal segmental glomerulosclerosis （iFSGS）. Methodology ： Our study population consisted of eighty-two Chinese patients with idiopathic FSGS and seventy volunteers as a normal control group. The genomic DNA was extracted from the peripheral blood cells of FSGS patients followed by polymerase chain reaction （PCR） and direct sequencing. The variances and SNPs were matched with genbank （www. ncbi. nlm. nih. gov; www. genometix, de; www. ensembl, org）. The expression of synaptopodin in patients＇ kidney tissue was investigated. The SNP association and the frequencies of genotypes were ana- lyzed followed by genotypes and phenotype analysis. Results：It was detected 5＇UTR single nucleotide heterozygous variance 1-24 G 〉 A in one patient, heterozygous variance 437 C 〉 T with amino-acid substitution （Pro146Leu） in second one, 1 903 A 〉 C with amino-acid substitution （Thr635Pro） in third patient, and also detected one variance 1 488 C 〉 T （Ihr496Ihr） with no amino-acid substitution. The same variances were not found in the control group of 70 healthy people. Matched with genbank these variances have not been reported. The expression of synaptopodin was reduced respectively in 1-24 G 〉A, 437 C 〉T（P146L） and 1 903 A 〉C（T635P） variant patients＇ kidney. We have not found that SNP loci were associated with FSGS. Conclusion：We detected SYNPO novel variances in sporadic patients with FSGS, which presumed that the SYNPO variances might play a role in pathogenesis of idiopathic FSGS.

关 键 词：局灶节段性肾小球硬化 SYNPO 变异 单核苷酸多态性 

分 类 号：R692.6[医药卫生—泌尿科学]