Epigenetics as a diagnostic and prognostic tool for pyeloureteral stenosis

OBJECTIVE: In the last few years, numerous studies have focused on the genetics of the renal system. Betchel et al in 2010 demonstrated that methylation, as a epigenetic phenomenon, would be involved in the perpetuation of fibrosis. In our study, we want to demonstrate whether epigenetics is related to pyeloureteral stenosis and, if that is the case, if it could be used as prognostic and diagnostic biomarker. METHODS: This is a descriptive observational and cross-sectional study that analyzed the methylation in DNA extracted from pyeloureteral junction samples obtained from surgery in pediatric patients in the period from 1999 to 2015, resulting in a total of 20 patients. Clinical data were analyzed using correlation tests and they were grouped with a free access software statistical phylogenetic package called PHYLIP. The selected genes for methylation-specific PCR (MSP) were the following: p 16, RASSF1A, MGMT, Cyclin D-2, HIN-1, E-Cadherin and RASAL-1. RESULTS: The clinical-radiological data analyzed phylogenetically by the PHYLIP program established 7 groups of patients. The results of methylation showed a considerable proportion of aberrant methylation in the promotor region of the genes p 16 (25%), MGMT (15%), E-Cadherin (25%), HIN-1 (25%) and RASAL-1 (35%). The association of the clinical-radiological groups with methylation/non-methylation states of each gene was also analyzed. CONCLUSIONS: This study demonstrates that methylation does have a role in fibrosis developed in pyeloureteral stenosis. Two clinical patterns of poor prognosis associated with two epigenetic methylation cluster. RAS-AL-1, E-Cadherin, HIN-1 and p16 would be candidates for future studies on their prognostic implications in pyeloureteral stenosis.