Differential methylation as a diagnostic biomarker of rare renal diseases: a systematic review

Abstract

Background The challenges in diagnosis of rare renal conditions can negatively impact patient prognosis, quality of life and result in significant healthcare costs. Differential methylation is emerging as an important biomarker for rare diseases and should be evaluated for rare renal conditions. Methods A comprehensive systematic review of methylation and rare renal disorders was conducted by searching the electronic databases MEDLINE, EMBASE, PubMed, Cochrane Library, alongside grey literature from GreyLit and OpenGrey databases, for publications published before September 2018. Additionally, the reference lists of the included papers were searched. Data was extracted and appraised including the primary focus, measurement and methodological rigour of the source. Eligibility criteria were adapted using the inclusion criteria from ‘The 100,000 Genomes Project’ and The National Registry of Rare Kidney Diseases, with additional focus on methylation. Results Thirteen full text articles were included in the review. Diseases analysed for differential methylation included glomerular disease, IgA nephropathy, ADPKD, rare causes of proteinuria, congenital renal agenesis, and membranous nephropathy. Conclusions Differential methylation has been observed for several rare renal diseases, highlighting its potential for improving molecular characterisation of these disorders. Further investigation of methylation following a standardised reporting structure is necessary to improve research quality. Multi-omic data will provide insights for improved diagnosis, prognosis and support for individuals living and working with rare renal diseases. Electronic supplementary material The online version of this article (10.1186/s12882-019-1517-5) contains supplementary material, which is available to authorized users.

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

“…Epigenetic signatures may display tissue specificity linked to disease mechanisms, however, obtaining kidney biopsy material is invasive and is not performed as part of routine clinical practice in people with DKD and T1D in the United Kingdom. Peripheral blood-based methylation biomarkers have shown promise in several clinical fields ( Moore et al, 2014 ; Agha et al, 2019 ; Cardenas et al, 2019 ; DiTroia et al, 2019 ; Henderson-Smith et al, 2019 ; Kerr et al, 2019a , b , 2020 ; Ladd-Acosta and Fallin, 2019 ; Zhou et al, 2019 ) including kidney disease ( Smyth et al, 2014b , 2018 ; Swan et al, 2015 ; Aranyi and Susztak, 2019 ; Gluck et al, 2019 ; Kato and Natarajan, 2019 ; Kerr et al, 2019b ; Park et al, 2019 ). We have previously demonstrated that blood-derived differential methylation is also reflected in kidney-derived differential methylation for CKD ( Smyth et al, 2014b ).…”

A New Genetic Insight for Orphan Renal Disorder, Fabry: A Review

“…4) V collagen and protein leakage has been reported in correlation with GFR and their presence in urine may be considered as the novelty for the diagnostic approach  Glomerular Protein-Microglobulin and N Glucosaminidase and Alanine aminopeptidase are the glomerular proteins and their dysfunction can be indicated as the sign of Fabry renal impairment (Fig. 4) [5].…”

“…Fabry disease is a rare renal disorder caused by mutation of the X-linked GLA gene which results in the deficiency of alpha-galactosidase [1]. The cells which are deficient in the alphagalactosidase enzyme can not metabolize glycosphingolipid mainly Globotriaosylceramide (GB 3 ) [2][3][4][5][6][7]. Accumulation of GB 3 can lead to various symptoms and for the progression of the cascade (series of progressive events) rather than deficiency of enzymes so maybe a diagnostic tool for the detection of Fabry disease [8].…”

Selective Triazenation Reaction (STaR) of Secondary Amines for Tagging Monomethyl Lysine Post‐Translational Modifications

“…Lysine methylation is one of the most important post‐translational modifications (PTMs) of proteins because it regulates various biological processes including cell growth, division, gene expression, and DNA/RNA binding [1–5] . Due to lysine's unique structure, it has the ability to undergo mono, di, and tri methylation, and different levels of methylation give rise to different functions and localization within a cell [6] . PTMs regulate cellular processes by influencing the interactions of proteins with other proteins, nucleic acids, and lipids.…”

“…[1][2][3][4][5] Due to lysinesu nique structure,i th as the ability to undergo mono, di, and tri methylation, and different levels of methylation give rise to different functions and localization within acell. [6] PTMs regulate cellular processes by influencing the interactions of proteins with other proteins,n ucleic acids,a nd lipids.W efocused our attention particularly on monomethyl lysine (Kme) PTM, which occurs on both histones and nonhistone proteins. [7][8][9][10][11] Kme PTMs have been implicated not only in transcriptional activation and silencing but the aberrant PTM levels have been linked to numerous diseases and disorders such as heart disease,cancer, and diabetes.…”