Saracyn M, Kisiel B, Franaszczyk M, Brodowska-Kania D, Żmudzki W, Małecki R, Niemczyk L, Dyrla P, Kamiński G, Płoski R, Niemczyk S. Diabetic kidney disease: Are the reported associations with single-nucleotide polymorphisms disease-specific?
World J Diabetes 2021;
12:1765-1777. [PMID:
34754377 PMCID:
PMC8554375 DOI:
10.4239/wjd.v12.i10.1765]
[Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/26/2021] [Accepted: 09/07/2021] [Indexed: 02/06/2023] Open
Abstract
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.
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