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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
Processing time: 210 Days and 22 Hours
BACKGROUND
The genetic backgrounds of diabetic kidney disease (DKD) and end-stage kidney disease (ESKD) have not been fully elucidated.
AIM
To examine the individual and cumulative effects of single-nucleotide polymorphisms (SNPs) previously associated with DKD on the risk for ESKD of diabetic etiology and to determine if any associations observed were specific for DKD.
METHODS
Fourteen SNPs were genotyped in hemodialyzed 136 patients with diabetic ESKD (DKD group) and 121 patients with non-diabetic ESKD (NDKD group). Patients were also re-classified on the basis of the primary cause of chronic kidney disease (CKD). The distribution of alleles was compared between diabetic and non-diabetic groups as well as between different sub-phenotypes. The weighted multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. The GRS distribution was then compared between the DKD and NDKD groups as well as in the groups according to the primary cause of CKD.
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 individual factors did not show any significant correlation. However, the GRS was significantly higher in patients with glomerular disease than in those with tubulointerstitial disease (P = 0.014) and in those with a combined group (tubulointerstitial, vascular, and cystic and congenital disease) (P = 0.018).
CONCLUSION
Our results suggest that selected SNPs that were previously associated with DKD may not be specific for DKD and may confer risk for CKD of different etiology, particularly those affecting renal glomeruli.
Core Tip: The genetic background of diabetic kidney disease (DKD) and end-stage kidney disease (ESKD) has not been fully elucidated. This study on a large population of dialyzed patients shows that single-nucleotide polymorphisms (SNPs) previously described in diabetes mellitus type 2 patients with DKD are not associated with the risk for ESKD of a diabetic background. Instead, the analyzed SNPs seem to correlate with glomerular kidney disease. These findings suggest that chronic kidney disease of different etiologies but the same dominant location of the pathological processes may share a common genetic background.
