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首页> 外文期刊>Gene: An International Journal Focusing on Gene Cloning and Gene Structure and Function >Characterization of NPHS2 gene polymorphisms associated to steroid resistance nephrotic syndrome in Indian children
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Characterization of NPHS2 gene polymorphisms associated to steroid resistance nephrotic syndrome in Indian children

机译：印度儿童类固醇抗性肾病患者的NPHS2基因多态性的表征

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Abstract Nephrotic syndrome (NS) is the common glomerular disease in children. These children are treated with steroids, depending upon their behavior. They are either steroid sensitive (SSNS) or steroid resistant (SRNS). NPHS2 gene mutants are linked to the risk of autosomal recessive SRNS and in some cases to SSNS. The present study has been performed to screen single nucleotide polymorphisms (SNPs) of the NPHS2 gene in a group of 90 Indian children suffering with NS (30 SSNS, 30 SRNS and 30 Controls) by PCR method followed by direct exon sequencing. Effect of SNPs on fold expression changes at transcript level of podocin was checked using quantitative real time PCR (qRT-PCR). SNPs identified through sequencing helps to carry out in-silico analysis. Overall 17 SNPs were identified in NPHS2 gene where 6 were found novel. Three missense SNPs p.R299Q, p.P20L and p.G35D were also identified in this population where SNP, p.G35D was found novel. In addition to sequencing analysis, results of in silico analysis shows that a mutant with these three missense SNPs has least ligand binding efficiency compared to native model. Moreover the significant observation of this study included two intronic SNPs c.451 + 23C T and c.451 + 58A T present in SRNS group of patients. These SNPs has shown high level of clinical significance within genomic and allelic frequency along with haplotypes and linkage disequilibrium count. The qRT-PCR analysis shows, down expression of podocin protein at transcript level in SRNS patients compared to SSNS patients. All these results support the fact that SNPs present in this population could affect the protein structural stability. Thus it is concluded that the polymorphisms predicted in this study might be disease causing in the NPHS2 gene and may have influence on the therapeutic response of NS patients. Highlights ? Sequencing analysis of NPHS2 gene found 35.29% novel and 64.7% known SNPs in Indian children with nephrotic syndrome. ? Comparative in silico analysis predicted that SNPs, p.R299Q, p.P20L and p.G35D could alter protein structural stability. ? qRT-PCR analysis revealed down-regulation of podocin transcript in individuals having SNPs. ]]>
机译：摘要肾病综合征（NS）是儿童常见的肾小球疾病。这些孩子是用类固醇治疗的，具体取决于他们的行为。它们是类固醇敏感（SSNS）或类固醇（SRNS）。 NPHS2基因突变体与常染色体隐性SRN的风险相关联，并且在某些情况下对SSNS进行连接。通过PCR方法筛选患有NS（30SSN，30SrNS和30对照）的90名印度儿童中NPHS2基因的单核苷酸多态性（SNP）对本发明的核苷酸多态性（SNP）进行了筛选，然后通过PCR方法进行直接外显子测序。使用定量实时PCR（QRT-PCR）检查SNP对雌霉素转录物水平的折叠表达的影响。通过测序识别的SNP有助于进行硅片分析。在NPHS2基因中鉴定了整体17个SNP，其中包含了6个新颖的。在这个人口中也发现了三个畸形SNPS p.R299Q，P.P20L和P.G35D，其中已发现SNP，P.G35D。除了测序分析外，硅分析的结果表明，与本地模型相比，具有这三个畸形SNP的突变体具有最小的配体结合效率。此外，该研究的显着观察包括两个内肠道SNPS C.451 + 23c＆ T和C.451 + 58a＆ T出现在SRNS组患者中。这些SNP在基因组和等位基因频率内显示出高水平的临床意义以及单倍型和连锁不平衡计数。与SSNS患者相比，QRT-PCR分析显示，在SRNS患者的转录物水平下表达豆荚蛋白蛋白表达。所有这些结果都支持这种人群中存在的SNP可能影响蛋白质结构稳定性。因此，得出结论，本研究预测的多态性可能是导致NPHS2基因的疾病，并且可能对NS患者的治疗反应产生影响。强调 ？ NPHS2基因的测序分析在印度肾病综合征中发现35.29％的新型和64.7％已知的SNP。还硅分析中的比较预测，SNP，P.R299Q，P.P20L和P.G35D可以改变蛋白质结构稳定性。还QRT-PCR分析揭示了在具有SNP的个体中的podocin转录物的下调。 ]]>

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