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

Rep Biochem Mol Biol. 2020 Jul;9(2):193-198. doi: 10.29252/rbmb.9.2.193.


Background: 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.

Methods: 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.

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). 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).

Conclusion: Methylation of the PKD1 promoter in ADPKD patients was inversely correlated with PKD1 expression.

Keywords: Autosomal Dominant Polycystic Kidney Disease (ADPKD); Epigenetic; Methylation; PKD1; methylation-sensitive high-resolution melt (MS-HRM) analysis.