Association Between Cannabinoid Receptor-1 Gene Polymorphism and the Risk of Diabetic Nephropathy Among Patients with Type 2 Diabetes Mellitus

Xuelian Zhang,1 Haiqing Zhu,2 Xiaoyan Xing,1 Chunyu Zhang3 1Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of China; 2Department of Endocrinology, Emergency General Hospital, Beijing 100028, People’s Republic of China; 3Department of Statistical Teaching and Research, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of ChinaCorrespondence: Xiaoyan XingDepartment of Endocrinology, China-Japan Friendship Hospital, Chaoyang District, Beijing 100029, People’s Republic of ChinaEmail 3382648198@qq.comBackground: The cannabinoid receptor 1 (CNR1) gene polymorphism is reportedly associated with components of metabolic syndrome and coronary artery diseases in patients with type 2 diabetes mellitus (T2DM). We investigated whether the common variant rs10493353 polymorphism is associated with diabetic nephropathy (DN) in T2DM patients.Patients and Methods: T2DM patients with DN were enrolled as a case group, and patients with only T2DM as a control group. Demographic data and biochemical parameters were collected. The polymerase chain reaction-based restriction fragment length polymorphism technique was used for genotyping. The odds ratio and 90% confidence interval were calculated to assess the association between genotypes and the risk of DN.Results: In total, 320 T2DM patients and 320 DN patients were enrolled. Compared with T2DM patients, the DN patients have a significantly larger body mass index (BMI), longer duration of disease, and higher proportions of smokers, drinkers, and hypertension. The risk of DN was significantly decreased by genotypes AA (OR=0.39, 95% CI=0.23– 0.67) and GA (OR=0.53, 95% CI=0.37– 0.75) vs GG (codominant model), GA/AA vs GG (OR=0.49, 95% CI=0.35– 0.67; dominant model), AA vs GG/GA (OR=0.47, 95% CI=0.28– 0.80; recessive model), and the A allele (OR=0.52, 95% CI=0.40– 0.68; allele model). Multiple logistic regressions still show significant levels. Negative interactions were found between gene and clinical parameters, including drinking, smoking, BMI, and hypertension.Conclusion: The A allele of CNR1 gene rs10493353 may be a protective factor for DN in T2DM patients. The risk factors of DN can affect the protective role of A allele in the progression of DN.Keywords: diabetes mellitus, diabetic nephropathy, gene polymorphism, cannabinoid receptor 1