Association of cannabinoid gene polymorphism with neutrophil gelatinaseassociatedlipocalin (NGAL), kidney injury molecule-1 (KIM-1) in type 2 diabetesmellitus with chronic kidney disease

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.