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Copyright (c) 2025 Maryam Z. Mohammed, Hiba M. Nasir, Nadia M.M Al-Shakir
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.Association of cannabinoid gene polymorphism with neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) in type 2 diabetes mellitus with chronic kidney disease
Corresponding Author(s) : Nadia M. M. Al-Shakir
Cellular and Molecular Biology,
Vol. 71 No. 10: Issue 10
Abstract
Diabetic kidney disease (DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM) and a leading cause of end-stage renal disease (ESRD). Genetic factors, including polymorphisms in the cannabinoid receptor 1 (CNR1) gene, may influence the risk and progression of chronic kidney disease (CKD) in diabetic patients. This study aimed to investigate the association of CNR1 gene polymorphisms, specifically single-nucleotide polymorphisms (SNPs) rs1049353 and rs1776966256, with serum levels of kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in Iraqi patients with T2DM, with and without CKD. A total of 120 subjects were enrolled and divided into three groups: 40 T2DM patients with CKD, 40 T2DM patients without CKD, and 40 healthy controls. Genotyping was performed using conventional polymerase chain reaction followed by Sanger sequencing. Serum NGAL and KIM-1 levels were measured by ELISA. Multiple novel CNR1 gene variants were detected and submitted to the NCBI database. The heterozygous GA genotype of rs1049353 was more prevalent in the CKD group compared to others, although not statistically significant. The rs773947953 (G>A) variant showed significant association with CKD, where the A allele appeared protective. Significant correlations were also observed between NGAL, KIM-1 levels, and specific SNP genotypes, including rs773947953 and new variations at positions 4217 (G>A) and 4224 (rs2481890897). These findings suggest that CNR1 gene polymorphisms influence susceptibility to diabetic kidney injury and are associated with elevated tubular injury markers. Identification of these genetic variations may help in early prediction and personalized management of DKD.
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