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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Diabetic kidney disease: Are the reported associations with single-nucleotide polymorphisms disease-specific?
Marek Saracyn, Bartłomiej Kisiel, Maria Franaszczyk, Dorota Brodowska-Kania, Wawrzyniec Żmudzki, Robert Małecki, Longin Niemczyk, Przemysław Dyrla, Grzegorz Kamiński, Rafał Płoski, Stanisław Niemczyk
Marek Saracyn, Dorota Brodowska-Kania, Wawrzyniec Żmudzki, Stanisław Niemczyk, Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw 04-141, Poland
Marek Saracyn, Dorota Brodowska-Kania, Grzegorz Kamiński, Department of Endocrinology and Isotope Therapy, Military Institute of Medicine, Warsaw 04-141, Poland
Bartłomiej Kisiel, Clinical Research Support Center, Military Institute of Medicine, Warsaw 04-141, Poland
Maria Franaszczyk, Department of Medical Biology, Molecular Biology Laboratory, Institute of Cardiology, Warsaw 04-628, Poland
Robert Małecki, Department of Nephrology, Międzyleski Specialist Hospital in Warsaw, Warsaw 04-749, Poland
Longin Niemczyk, Department of Nephrology, Dialysis and Internal Diseases, Warsaw Medical University, Warsaw 02-097, Poland
Przemysław Dyrla, Department of Gastroenterology, Military Institute of Medicine, Warsaw 04-141, Poland
Rafał Płoski, Department of Medical Genetics, Medical University of Warsaw, Warsaw 02-106, Poland
Author contributions: Saracyn M, Kisiel B, Płoski R and Niemczyk S designed the study; Saracyn M, Brodowska-Kania D, Żmudzki W, Niemczyk L and Małecki R collected clinical data and blood samples; Franaszczyk M and Saracyn M, isolated DNA; Franaszczyk M and Płoski R genotyped SNP’s; Kisiel B performed statistical analysis; Saracyn M, Kisiel B, Dyrla P, Kamiński G, Płoski R and Niemczyk S interpreted clinical and genetical data; Saracyn M, Kisiel B and Brodowska-Kania D searched literature; SaracynM, Kisiel B, Płoski R and Niemczyk S prepared the manuscript; all authors contributed to final writing, proof-reading of the manuscript; all authors approved the final version of the paper.
Supported by Ministry of Science and Higher Education Grant, No. 171/12.
Institutional review board statement: This study was approved by the Military Institute of Medicine Ethics Committee, Warsaw, Poland (approval No. 5/WIM/2010).
Informed consent statement: All involved patients gave their informed consent.
Conflict-of-interest statement: The authors declare that they have no competing financial interests. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at msaracyn@interia.pl.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Marek Saracyn, MD, PhD, Associate Professor, Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, 128 Szaserów Street, Warsaw 04-141, Poland. msaracyn@interia.pl
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: May 3, 2021
Revised: May 26, 2021
Accepted: September 7, 2021
Article in press: September 7, 2021
Published online: October 15, 2021
ARTICLE HIGHLIGHTS
Research background
A diabetes mellitus (DM) epidemic is underway; 40% patients with type 2 DM (DM2) develop a serious complication, diabetic kidney disease (DKD), and the occurrence of DKD considerably worsens the long-term prognosis. However, the genetic backgrounds of DKD and end-stage kidney disease (ESKD) have not been fully elucidated.
Research motivation
Previous studies have searched for associations between genetic markers and the risk of diabetic renal complications but may have overlooked a critical issue: whether these genetic markers are specific for DKD or are, rather, associated with the risk for chronic kidney disease and ESKD itself, regardless of its explicit underlying cause.
Research objectives
The aim of our study was to examine the individual and cumulative effects (as a genetic risk score, GRS) of SNPs previously described in DM2 patients with DKD on the risk of diabetic ESKD in a population of hemodialyzed patients and to determine if any associations observed were specific for DKD.
Research methods
Fourteen SNPs were genotyped in 136 patients with diabetic ESKD (DKD group) and 121 patients with non-diabetic ESKD (NDKD group). Patients were also classified on the basis of the KDIGO guidelines and CKD classification system based on the primary cause of CKD, such as glomerular disease (GD), tubulointerstitial disease (TID), vascular disease (VD), and cystic and congenital disease (CCD). Patients with complex pathogenesis (CP) were considered separately. The distribution of alleles was compared between diabetic and non-diabetic groups as well as between different sub-phenotypes. The weighted multilocus GRS was calculated to estimate the cumulative risk conferred by all SNPs. The distribution of GRS was then compared between the DKD and NDKD groups as well as in the groups according to KDIGO guidelines.
Research results
One SNP (rs841853; SLC2A1) showed a nominal association with DKD (P = 0.048; P > 0.05 after Bonferroni correction). The GRS was higher in the DKD group (0.615 ± 0.260) than in the NDKD group (0.590 ± 0.253), but the difference was not significant (P = 0.46). The analysis of associations between GRS and the individual factors of gender, diuresis, and rate of CKD progression in either study group did not show any significant correlation. However, the GRS was significantly higher in the GD group than in the TID group (P = 0.014) and the combined TID+VD+CCD group (P = 0.018).
Research conclusions
Our study may be the first to demonstrate that selected SNPs that were previously associated with DKD may not be specific for DKD and may confer genetic risk for CKDs of different etiologies, particularly those affecting renal glomeruli.
Research perspectives
Further studies are needed to confirm a similar correlation of other SNPs previously associated with DKD with the development and etiology of ESKD.
