DNA methylation changes between relapse and remission of minimal change nephrotic syndrome

Yasuko Kobayashi,Akihiro Morikawa,Izuho Hatada,Kenichi Maruyama,Yuka Ikeuchi,Hirokazu Arakawa,Chikage Yoshizawa,Hiromi Horiguchi,Toshio Watanabe,Akira Aizawa,Takumi Takizawa,Satoko Kakegawa

doi:10.1007/s00467-012-2248-z

Yasuko Kobayashi, Akihiro Morikawa + Show 10 more

Open Access

https://doi.org/10.1007/s00467-012-2248-z

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Journal: Pediatric Nephrology	Publication Date: Aug 2, 2012
Citations: 41	License type: cc-by

Affiliation: Gunma University, Gunma Chuo Hospital

Abstract

BackgroundDNA 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).MethodsGenome-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.ResultsThree 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00467-012-2248-z) contains supplementary material, which is available to authorized users.

Highlights

The distance distribution from the regression line of all probes in microarray-based integrated analysis of methylation by isochizomers (MIAMI) was significantly different between monocytes and Th0s
Our results demonstrate that the change in DNA methylation patterns from remission to relapse in minimal change nephrotic syndrome (MCNS) occurs predominantly in Th0s rather than in monocytes and suggest that epigenetic regulation in Th0s underlies the pathogenesis of MCNS
Epigenetics is the study of mitotically heritable changes in gene expression that occur without direct DNA sequence alterations

Summary

Introduction

Epigenetics is the study of mitotically heritable changes in gene expression that occur without direct DNA sequence alterations. Minimal change nephrotic syndrome (MCNS) is the most common cause of nephrotic syndrome in children and is characterized by massive proteinuria and hypoalbuminemia in a relapse/remission course without histological evidence of immune-mediated inflammatory damage. These manifestations are typically reversible with the use of corticosteroid therapy. Since the characteristic features of MCNS include (1) a recurrent relapse/remission course, (2) gender preference, (3) age preference of onset and relapse, and (4) steroid response in most patients, a genetic defect cannot explain the pathogenesis of this disease; epigenetic alterations may occur without a direct change in the genetic sequence.

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