The Study of the Correlation Between Cannabinoid Receptor-1 Gene Polymorphisms and Risk of Diabetic Nephropathy in Iraqi People

Authors

  • Raghda Hisham Aljorani Department of Clinical Laboratory Sciences, College of Pharmacy, University of Baghdad,
  • Eman Saadi Saleh Department of Clinical Laboratory Sciences, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.31351/vol34iss1pp1-9

Keywords:

Cannabinoid receptor-1, Diabetes mellitus, Diabetic nephropathy, Gene polymorphism

Abstract

Background: Cannabinoid receptor-1 (CNR1) gene polymorphism is reportedly associated with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). It has been confirmed that CNR1 plays an important role in the peripheral organs, including the kidneys. Alterations of cannabinoid receptor expression and activity have been discovered in various renal diseases such as diabetic nephropathy. The goal is to find out if the CNR1 genetic variations rs750464422 T/C and rs1776965150 T/A affect how likely T2DM Iraqi patients are to get DN. Methods: In this cross-sectional study, we included 100 patients who have had T2DM. We classified the participants into two groups: the first group was comprised of 50 patients with DN (the case group), and the second group was comprised of 50 patients without DN (the control group). CNR1 rs rs750464422, and rs1776965150 polymorphisms were genotyped in DN patients and controls by polymerase chain reaction (PCR). Results: Data analysis revealed that there was a significant difference in the frequencies of the TC genotypes of CNR1 rs750464422 between patients with DN and controls (p=0.001), while there were non-significant differences in the distribution of CC genotypes (p=0.6). Moreover, the C allele of this polymorphism was associated with an increased risk of DN compared to the T allele (p=0.001, OR=3.29 and 95% CI= 1.58-7.07). We predicted that patients with the rs1776965150 genetic polymorphism have a significant difference in the TA genotype (p=0.05, OR= 0.95, and 95% CI= 0.1-1.10), while the A allele frequency shows a non-significant difference (p=0.2). Conclusion: CNR1 genetic variations, rs750464422 polymorphisms, were correlated with the development of DN, while rs1776965150 polymorphisms were not associated with DN

How to Cite

1.
Raghda Hisham Aljorani, Eman Saadi Saleh. The Study of the Correlation Between Cannabinoid Receptor-1 Gene Polymorphisms and Risk of Diabetic Nephropathy in Iraqi People. Iraqi Journal of Pharmaceutical Sciences [Internet]. 2025 Mar. 29 [cited 2025 Apr. 1];34(1):1-9. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2878

Publication Dates

Received

2023-08-14

Revised

2023-08-24

Accepted

2023-11-16

Published Online First

2025-03-29

References

Salih BH, Ali SH, Allehibi KI. Serum Aldosterone Levels in Patients with Diabetic Nephropathy in Relation to Vascular Calcification. Iraqi Journal of Pharmaceutical Sciences. 2019;28(1):53-63.

Hussein AM, Ali SH, Rahma AM, Al-Shami AA. Anemia in diabetic patients without microalbuminuria in relation to type of diabetes, glycemic control, and hs-C reactive protein levels. Al-Nahrain Journal of Science. 2010;13(3):110-119.

Salman O, Merdaw MA, Almaliky AA. A Novel Single Nucleotide Polymorphism of Interleukin-10 Gene is Linked to Type 2 Diabetes Mellitus in Iraqi Patients with Toxoplasmosis (Conference Paper). Iraqi Journal of Pharmaceutical Sciences. 2022;31(Suppl.):1-8.

Crasto, W, Patel V, Davies MJ, Khunti K. Prevention of microvascular complications of diabetes. Endocrinology and Metabolism Clinics. 2021;50(3):431-455.‏

Horváth B, Mukhopadhyay P, Haskó G, Pacher P. The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications. The American Journal of Pathology. 2012;180(2):432-442. https://doi.org/10.1016/j.ajpath.2011.11.003

Tam J. The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases. Journal of Basic and Clinical Physiology and Pharmacology. 2016;27:267-276.

Ameen IA, Saleh ES, Mhaibes SH, Taha KN, Dawood DAH, Hawaa Salman Kamil HS. Evaluation of Some Inflammatory Cytokines and Glycated Hemoglobin in Uncontrolled Type 2 Diabetes Mellitus with Nephropathy. Indian Journal of Forensic Medicine & Toxicology. 2020;14(2), 1628-1632. https:// doi.org /10. 37 5 06/ijfmt.v14i2.3158

Mohammed MM, Hadi RA, Salman IN. Potential Positive Effects using Coenzyme Q10 Supplement as Adjuvant Therapy to Gabapentin for Managing Diabetic Neuropathy. Iraqi Journal of Pharmaceutical Sciences. 2022;31(2):177-183.

Mahmood AR. Estimation of oxidative stress and some trace elements in Iraqi men patients with type 2 diabetes mellitus. Iraqi Journal of Pharmaceutical Sciences. 2016;25(1):17-22.‏

Mukhopadhyay P, Pan H, Rajesh M, Bátkai S, Patel V, Harvey-White J, et al. CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model. Br J Pharmacol. 2010;160(3):657-668. doi: 10.1111/j.1476-5 3 81.2010.00769.x.

Saleh Khudhur S, Saadi Saleh E, Hadi Alosami MG, Shareef L. Association between polymorphisms within the gene coding for tumor necrosis factor (TNF)-alpha with outcomes of treatment in a sample of Iraqi patients with ankylosing spondylitis taking etanercept: an observational study. F1000Research. 2022;11:1576.‏

Pucci M, Zaplatic E, Micioni Di Bonaventura MV, Micioni Di Bonaventura E, De Cristofaro P, Maccarrone M, et al. On the Role of Central Type-1 Cannabinoid Receptor Gene Regulation in Food Intake and Eating Behaviors. International Journal of Molecular Sciences 2021;22(1):398. https://doi.org/10.3390/ijms22010398.

Zhang X, Zhu H, Xing X, Zhang C. Association Between Cannabinoid Receptor-1 Gene Polymorphism and the Risk of Diabetic Nephropathy Among Patients with Type 2 Diabetes Mellitus. Pharmgenomics Pers Med. 2020;13:591-599. doi:10.2147/PGPM.S278897

Rizvi S, Raza ST, Mahdi F. Association of genetic variants with diabetic nephropathy. World J Diabetes. 2014;5(6):809-816. doi:10.4239/wjd.v5.i6.809.

Glover T, Mitchell K. An introduction to Biostatistics, 2nd ed. Waveland press Inc., 2008..

Forthofer RN, Lee ES. Introduction to biostatistics: a guide to design, analysis, and discovery. Elsevier, 2014

Ali SA, ALsharifi ZAR, Allawi AAM. The Impact of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Iraqi Patients with Diabetic Nephropathy. International Journal of Psychosocial Rehabilitation. 2020;24(02).‏

Salih RKM, Al-Gharawi AM, Al-Lehibi KI. The Correlation Between Hyperglycemia and Rheumatoid Factor in Type 2 Diabetic Patients in Al-Rusafa Area, Baghdad. Iraqi Journal of Pharmaceutical Sciences. 2012;21(1):105-111.‏

Jourdan T, Szanda G, Rosenberg A, Tam J, Earley BJ, Godlewski G, et al. Overactive cannabinoid 1 receptor in podocytes drives type 2 diabetic nephropathy. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(50):E5420–E5428. https://doi.org/10.1073/pnas.1419901111

Wu T, Ding L, Andoh V, Zhang J, Chen L. The Mechanism of Hyperglycemia-Induced Renal Cell Injury in Diabetic Nephropathy Disease: An Update. Life (Basel, Switzerland) 2023 ;13 (2):539. https://doi.org/10.3390/life13020539

Buraczynska M, Wacinski P, Zukowski P, Dragan M, Ksiazek A. Common polymorphism in the cannabinoid type 1 receptor gene (CNR1) is associated with microvascular complications in type 2 diabetes. Journal of Diabetes and its Complications. 2014;28(1):35-39. https://doi .org/10.1016/j.jdiacomp.2013.08.005

Doris, Joseph M., et al. "Genetic polymorphisms of the endocannabinoid system in obesity and diabetes." Diabetes, Obesity and Metabolism (2019) 21.2: 382-387.

Downloads

Published

2025-03-29