Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pathology, University of California, Los Angeles, USA.
BMC Med Genomics. 2022 May 11;15(1):109. doi: 10.1186/s12920-022-01265-1.
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.
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).
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).
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.
复发性肾结石的形成是一个主要的医学问题，给全球的医疗保健和经济带来了巨大的负担。环境和遗传因素与更大的肾结石形成风险有关。我们旨在评估三个靶基因中甲基化在复发性结石形成中的作用。
我们旨在检查维生素 D 受体（VDR）、钙敏感受体（CaSR）和紧密连接蛋白 14（CLDN14）基因启动子超甲基化与复发性肾结石之间的关联。我们招募了 30 名连续复发性肾结石患者（18-60 岁）（病例）和 30 名年龄和性别匹配的对照。为了鉴定启动子甲基化，在采集血液和提取 DNA 后，对每个候选基因的两个靶区域进行双硫代。通过甲基化特异性高分辨率熔化（MS-HRM）进行甲基化定量。
患者和对照组的平均年龄（平均值±标准差）分别为 49.58±14.23 岁和 BMI 36.12±2.72。当考虑三个未甲基化、甲基化和超甲基化簇的甲基化状态时，结石形成组与对照组之间所有六个靶区域的甲基化状态均有显著差异。与 CasR 相比，VDR 和 CLDN 的影响更高（p 值<0.001 和<0.005 与 p 值<0.256）。
作为一种重要的表观遗传机制，甲基化在复发性结石形成中应得到更多的考虑。VDR 和 CLDN 基因启动子的高甲基化可能在复发性肾结石形成中起重要作用。
