The Methylation Profile of IFN-γ, SOCS1 and SOCS3 Promoter Regions in End-Stage Renal Disease

Maivel Ghattas Fatma El-shaarawy

doi:10.4172/2153-0602.1000144

Abstract

End-stage renal disease (ESRD) is a state of chronic inflammation. DNA methylation is a major epigenetic modification that has the potential to silence gene expression. IFN-γ and suppressor of cytokine signaling (SOCS) are essential modulators of inflammation. The current study aimed to determine the methylation status of IFN-γ, SOCS1 and SOCS3 promoter regions in DNA isolated from peripheral blood of ESRD patients and controls, in order to correlate this methylation status with the clinical features of ESRD. Ninety six ESRD patients and 96 healthy ethnically, age and gender matched controls were included in the study. The promoter methylation of the studied genes was assessed using the methylation-specific polymerase chain reaction (MSP). Most of our samples were positive for IFN-γ promoter methylation. Full unmethylation was observed only in the ESRD group (7.3%), and statistical difference was observed among groups (P=0.02). IFN-γ unmethylation was associated to a decrease in estimated glomerular filtration rate (eGFR) and an increase in both serum creatinine and total cholesterol levels. For SOCS1 promoter methylation, partial and full methylation were observed only in ESRD patients (5.2% and 2.1%, respectively); however no methylation was detected in controls (P=0.014). SOCS3 promoter methylation was not detected in either the patient or control group. In conclusion, the methylation profile of IFN-γ and SOCS1 promoter regions play an important role in the pathogenesis of ESRD. The present study highlights the role of epigenetics in disease progression.

Highlights

End-stage renal disease (ESRD) patients have been continuous markedly increased morbidity and mortality worldwide despite the development in renal replacement therapy [1]
The ESRD patients maintained on hemodialysis with a median duration of 35.5 months
Inflammation is common in chronic kidney disease (CKD) and worsens as the disease progresses towards ESRD [6], where the overproduced proinflammatory cytokines may play a significant role in renal injury [43]

Summary

Introduction

End-stage renal disease (ESRD) patients have been continuous markedly increased morbidity and mortality worldwide despite the development in renal replacement therapy [1]. In Egypt, the prevalence of ESRD in 2008 was 483 per million population [2] and this prevalence is presumed to be increasing [3]. It is well established that ESRD is a state of chronic systemic inflammation [4], which is attributed to both dialysis-related and dialysis-unrelated factors [5]. The difference between individuals in the progression to ESRD may be due to differences in the genetic susceptibility [7]. The prevalence of inflammation in patients with chronic kidney disease (CKD) varies significantly between ethnic groups, suggesting that genetic factors may be a major contributory factor for the development of systemic inflammation [8]

Objectives

Methods

Results

Conclusion