The Correlation Between Promoter Hypermethylation of VDR, CLDN, and CasR Genes and Recurrent Stone Formation

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2022 May 13

PMID 35546405

Authors

Fatemeh Khatami

Alireza Gorji

Mahdi Khoshchehreh

Rahil Mashhadi

Mahin Ahmadi Pishkuhi

Alireza Khajavi

Alireza Namazi Shabestari

Seyed Mohammad Kazem Aghamir

Affiliations

Soon will be listed here.

Abstract

Objectives: Recurrent Kidney stone formation is a main medical problem imposing a significant burden on both healthcare and the economy worldwide. Environmental and genetic factors have been linked to a bigger risk of kidney stone formation. We aim to assess the role of methylation on recurrent stone formation in three target genes.

Methods: We aimed to check the association between promoter hypermethylation vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and claudin 14 (CLDN14) genes in recurrent kidney stones. We enrolled 30 consecutive recurrent kidney stone formers (age 18-60 years) (cases) and 30 age and gender-matched controls.3. To identify promoter methylation, two target regions from each candidate gene were bisulfited after blood collection and DNA extraction. Methylation quantification was done through methylation-specific high resolution melting (MS-HRM).

Results: The mean age of the patients and controls (mean ± SD) was 49.58 ± 14.23 years and BMI 36.12 ± 2.72. The methylation status in all six target regions was meaningfully different between the stone-former group and controls when methylation was considered in three clusters of unmethylated, methylated, and hypermethylated. A higher effect in VDR and CLDN was observed compare to CasR (p-value < 0.001, and < 0.005 versus p-value < 0.256).

Conclusions: Methylation as an important epigenetic mechanism should be considered more in recurrent stone formations. Promoter hypermethylation of VRD and CLDN genes may have an essential role in recurrent kidney stones formations.

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