Methylation of the PKD1 Promoter Inversely Correlates with its Expression in Autosomal Dominant Polycystic Kidney Disease.

Sajjad Biglari,Nasim Sohrabifar,Sayyed Mohammad Hossein Ghaderian,Mohammad Hassan Ghadiani,Mandana Hasanzad,Mohsen Nafar,Hossein Jafari,Fatemeh Hajirezaei

doi:10.29252/rbmb.9.2.193

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), a multisystem disorder, is the most prevalent type of hereditary kidney disease. Here, we aimed to evaluate methylation of the PKD1 gene (PKD1) promoter and its correlation with PKD1 expression in peripheral blood. In this case-control study methylation of the PKD1 promoter was evaluated using methylation-sensitive high-resolution melt (MS-HRM) analysis. PKD1 expression was assessed by quantitative real-time PCR. The correlation was evaluated using the Pearson correlation test. Twenty subjects from both the patient and control groups (n= 40 for each) were methylated at the PKD1 promoter to various levels (18.9% in patients and 62.5% in controls). This difference was statistically significant (p< 0.0001). PKD1 expression in blood samples was significantly greater in ADPKD patients than in controls (p= 0.0081). Significant correlation was seen between PKD1 expression and its promoter methylation status in peripheral blood (r case= -0.5300, p= 0.0162, and r control = -0.6265, p= 0.0031). Methylation of the PKD1 promoter in ADPKD patients was inversely correlated with PKD1 expression.

Highlights

Autosomal dominant polycystic kidney disease (ADPKD), a ciliopathy with high morbidity and mortality, is the most prevalent type of hereditary kidney disease, affecting one per 400-1000 individuals
In this study we evaluated 40 ADPKD patients of both genders with deleterious mutations in PKD1 or PKD2 with mean ages of 27.8 and 27 years for males and females, respectively, and 40 controls with mean ages of 42.1 and 57.1 years, for males and females, respectively
The mean percentage of methylation of the PKD1 promoter was significantly greater in patients aged 15-30 years and 31-60 years than in controls of the same age groups (p= 0.01 and 0.001, respectively)

Summary

Introduction

Autosomal dominant polycystic kidney disease (ADPKD), a ciliopathy with high morbidity and mortality, is the most prevalent type of hereditary kidney disease, affecting one per 400-1000 individuals. We aimed to evaluate methylation of the PKD1 gene (PKD1) promoter and its correlation with PKD1 expression in peripheral blood. Results: Twenty subjects from both the patient and control groups (n= 40 for each) were methylated at the PKD1 promoter to various levels (18.9% in patients and 62.5% in controls). This difference was statistically significant (p< 0.0001). Significant correlation was seen between PKD1 expression and its promoter methylation status in peripheral blood (r case= -0.5300, p= 0.0162, and r control = -0.6265, p= 0.0031). Conclusions: Methylation of the PKD1 promoter in ADPKD patients was inversely correlated with PKD1 expression

Objectives

Methods

Results

Conclusion