Iraqi researchers found novel variants in the cannabinoid receptor 1 gene among diabetic patients with kidney disease, though the specific variants tested weren't significantly linked to kidney injury biomarkers.
Genetics researchers studying the endocannabinoid system, nephrologists interested in novel CKD risk factors, and scientists exploring cannabinoid receptor biology.
What the researchers found
This study explored whether genetic variations in the cannabinoid receptor 1 (CNR1) gene—part of the endocannabinoid system—are associated with kidney damage in people with type 2 diabetes.
The researchers genotyped 120 subjects divided into three groups: 40 diabetic patients with chronic kidney disease (CKD), 40 diabetic patients without CKD, and 40 healthy controls. They looked at two specific genetic variants (SNPs) in the CNR1 gene and measured blood levels of two kidney injury biomarkers: NGAL and KIM-1.
The main finding was mixed. The heterozygous GA genotype of one variant (rs1049353) was more common in the CKD group, but the difference wasn't statistically significant. However, the study did discover multiple novel CNR1 gene variants that were submitted to the NCBI database—a contribution to the basic science of endocannabinoid genetics even if the clinical association didn't reach significance.
The theoretical basis is sound: the endocannabinoid system is involved in kidney physiology and inflammation, so genetic variations in cannabinoid receptors could plausibly influence how diabetes damages the kidneys. But this small study couldn't establish that connection definitively.
Why it matters
The endocannabinoid system is increasingly recognized as playing roles in metabolic disease and kidney function. If specific cannabinoid receptor gene variants predispose diabetic patients to kidney damage, that could eventually inform both genetic screening and therapeutic targeting. This study is a small first step in that direction for an Iraqi population.
The numbers in context
N = 120 (40 T2DM + CKD, 40 T2DM only, 40 controls). GA genotype of rs1049353 more prevalent in CKD group but not statistically significant. Multiple novel CNR1 variants discovered and submitted to NCBI.
How the study worked
Case-control study of 120 Iraqi subjects: 40 T2DM + CKD, 40 T2DM without CKD, 40 healthy controls. Genotyping of CNR1 SNPs rs1049353 and rs1776966256 via PCR and Sanger sequencing. Serum NGAL and KIM-1 measured by ELISA.
Who was studied
N=120 Iraqi adults, 40 with type 2 diabetes and chronic kidney disease, 40 with type 2 diabetes without chronic kidney disease, and 40 healthy controls.
What this study cannot tell us
Small sample size (40 per group) likely underpowered to detect modest genetic effects. Single-center Iraqi population limits generalizability. Only two SNPs examined out of many possible CNR1 variants. Cross-sectional design can't establish causation. The non-significant primary finding means the hypothesis remains unconfirmed.
How to read the evidence
Small case-control genetic study with non-significant primary results—hypothesis-generating for the endocannabinoid-kidney disease connection.
When this study was published
Published in 2025 with data from an Iraqi population, contributing to global genetic diversity in cannabinoid research.
The bigger picture
This connects to the broader understanding of the endocannabinoid system beyond recreational cannabis use. RTHC-00005 described the discovery of anandamide, and RTHC-00006/00009/00013 explored CB1 receptor function at the molecular level. This study extends that basic science into clinical genetics, asking whether natural variation in endocannabinoid genes affects disease outcomes—a question that could eventually influence personalized medicine approaches.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Would larger studies with more statistical power find significant associations between CNR1 variants and diabetic kidney disease? Do the novel CNR1 variants discovered here have functional significance? Could endocannabinoid-targeted therapies protect against diabetic kidney damage?
Read the original research
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.
Cellular and molecular biology (Noisy-le-Grand, France), 71(10), 101-110
Cellular and Molecular Biology is a peer-reviewed journal known for publishing research in the field of cellular and molecular biology.
Citation
Mohammed, Maryam Z; Nasir, Hiba M; Al-Shakir, Nadia M M. (2025). 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.. Cellular and molecular biology (Noisy-le-Grand, France), 71(10), 101-110. https://doi.org/10.14715/cmb/2025.71.10.14
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