title: Genetic effect of the NPHS2 gene variants on proteinuria in minimal change disease and immunoglobulin A nephropathy.
abstract: BACKGROUND
  Proteinuria varies in different glomerular diseases and even the same one. Podocin, encoded by gene NPHS2, is important in maintaining the integrity of slit diaphragm structure and avoiding proteinuria. Presently, case-control association studies were performed to investigate the genetic effect of variants in NPHS2 in a mass proteinuric glomerulopathy, minimal change disease (MCD) at first, followed by further investigation in immunoglobulin A nephropathy (IgAN).
  
  
  METHODS
  At first, 214 northern Chinese patients with MCD and 493 geographically-matched healthy controls were enrolled. Variants of the NPHS2 were screened. SNP-2 (rs3829795:C>T, c.-670C>T) and SNP-5 (rs3738423:C>T, c.288C>T) were selected as tagging single nucleotide polymorphisms (SNP) and haplotypes were reconstructed. Association was analyzed in MCD patients. Then, the identified SNP site was analyzed in IgAN patients with mild histological changes (Haas subclass I and II).
  
  
  RESULTS
  The C allele and CC genotype frequencies at the SNP-2 site, as well as the frequency of haplotype CC, were significantly lower in MCD patients than in healthy controls. Furthermore, they were also associated with the degree of proteinuria in MCD patients. But in IgAN patients, no such association was identified.
  
  
  CONCLUSIONS
  The study suggested the polymorphism and haplotype of NPHS2 gene were associated with the genetic susceptibility and also the degree of proteinuria to MCD. Proteinuria in MCD and IgAN might occur through different mechanisms.
authors.affiliation: Renal Division, Department of Internal Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Chen-Dan
authors.initials: CD
authors.lastname: Wang
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Lv
authors.forename: Gui-Sen
authors.initials: GS
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wang
mesh_terms: D016022:Case-Control Studies; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D009402:Nephrosis, Lipoid / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011507:Proteinuria / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein