title: DNA methylation changes between relapse and remission of minimal change nephrotic syndrome.
abstract: BACKGROUND
  DNA methylation of gene promoters is associated with transcriptional inactivation. Changes in DNA methylation can lead to differences in gene expression levels and thereby influence disease development. We hypothesized that epigenetics underlies the pathogenesis of minimal change nephrotic syndrome (MCNS).
  
  
  METHODS
  Genome-wide DNA methylation changes between relapse and remission in monocytes (n = 6) and naive T helper cells (Th0s) (n = 4) isolated from patients with MCNS were investigated using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. We confirmed the MIAMI results using bisulfite-pyrosequencing analysis. Expression analysis was performed using quantitative real-time PCR.
  
  
  RESULTS
  Three gene loci (GATA2, PBX4, and NYX) were significantly less methylated in Th0s during relapse than in remission, compared to none in monocytes. In addition, the distance distribution from the regression line of all probes in MIAMI was significantly different between monocytes and Th0s. The mRNA levels of the three genes in Th0s were not significantly different between relapse and remission.
  
  
  CONCLUSIONS
  Our results demonstrate that the change in DNA methylation patterns from remission to relapse in MCNS occurs predominantly in Th0s rather than in monocytes and suggest that epigenetic regulation in Th0s underlies the pathogenesis of MCNS.
authors.affiliation: Department of Pediatrics, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. kobayasu@gunma-u.ac.jp
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Aizawa
authors.forename: Takumi
authors.initials: T
authors.lastname: Takizawa
authors.forename: Chikage
authors.initials: C
authors.lastname: Yoshizawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Horiguchi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ikeuchi
authors.forename: Satoko
authors.initials: S
authors.lastname: Kakegawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kenichi
authors.initials: K
authors.lastname: Maruyama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Morikawa
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Arakawa
mesh_terms: D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009402:Nephrosis, Lipoid / Q000235:genetics* / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012075:Remission, Spontaneous; D017422:Sequence Analysis, DNA; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*