Association of Cannabinoid CB2 Receptor Q63R Variant With Rheumatoid Arthritis in an Iranian Cohort

<b>Background:</b> Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily affecting the joints. The endocannabinoid system plays a crucial role in maintaining immune balance by regulating immune functions. Variations in the CB2 receptor gene (<i>CNR2</i>) can disrupt intracellular signaling, impairing the regulatory functions of endocannabinoids. This dysfunction is associated with an imbalanced immune response and an increased risk of autoimmune inflammatory disorders. This study investigates, for the first time in an Iranian population, the association between the Q63R polymorphism in the <i>CNR2</i> gene and RA. <b>Methods:</b> A total of 120 RA patients and 120 healthy controls were genotyped using the TaqMan assay. Demographic and clinical data, including gender, age, and ethnicity, were collected through questionnaires. The codominant, dominant, recessive, overdominant, and additive inheritance models were analyzed using SNPStats software. <b>Results:</b> Logistic regression analysis revealed significant associations under the codominant, dominant, and additive inheritance models, with RR genotype carriers exhibiting more than a 2.5-fold increased risk of developing RA. <b>Conclusion:</b> The findings of this study suggest a potential role of the <i>CNR2</i> gene in RA susceptibility among Iranian patients. However, further large-scale studies are required to better understand the contribution of the CB2 receptor to disease susceptibility and its potential clinical applications as a biomarker for diagnosis and therapeutic interventions.