Study of cannabinoid receptor 2 Q63R gene polymorphism in Lebanese patients with rheumatoid arthritis

Abstract

The cannabinoid (CB) receptor 2, primarily expressed in immune cells, was shown to play important immune-regulatory functions. In particular, the CB2-R63 functional variant has been shown to alter the ability of the CB2 receptor to exert its inhibitory function on T lymphocytes. The aim of this study was to investigate the association between a common dinucleotide polymorphism, Q63R, in the cannabinoid receptor 2 gene (CNR2) and rheumatoid arthritis (RA) in the Lebanese population. One hundred five unrelated Lebanese RA patients and one hundred five controls from different Lebanese governorates were recruited in this study. Genomic DNA was extracted, polymerase chain reaction was performed, and CNR2 was genotyped in a blinded fashion. The χ test was used to determine the differences in genotypes and allele frequencies. CNR2 genotyping showed significantly higher frequencies of the CB2-R63 variant (allele frequencies, P < 0.00001; genotype distribution, P < 0.00001) in RA patients when compared with healthy controls. Moreover, RR carriers had more than 10-fold risk for developing RA (OR = 10.8444, 95% CI = 5.0950-23.0818; P < 0.0001), and QR carriers had more than 3-fold risk (OR = 3.8667, 95% CI = 1.7886-8.3591; P = 0.0006) as compared with QQ carriers. Our preliminary results suggest a role of CB2-Q63R gene polymorphism in the etiology of RA, thus supporting its potential use as a pharmacological target for selective agonists in clinical practice.

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

“…This finding demonstrates the potential role of cannabinoids in OA treatment. The CB 2 receptor gene polymorphism Q63R is associated with increased arthritis risk [ 107 , 108 ]. CB 2 is also important for the regulation of osteoblast differentiation and bone formation.…”

Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking

“…An association between the CB2-Q63R variation and autoimmune conditions such as thrombocytopenic purpura [ 47 ], celiac disease [ 25 ], juvenile idiopathic arthritis [ 21 ], inflammatory bowel disease [ 48 ], and rheumatoid arthritis [ 24 ] has been reported. The data from our previous study suggested an involvement of the Q63R variation in susceptibility to multiple sclerosis in Iranian patients [ 20 ].…”

Cannabinoid CB2 Receptor Functional Variation (Q63R) is Associated with COVID-19 Severity: from Human Study to Molecular Docking

“…The association between the CB2-Q63R variation and autoimmune conditions such as thrombocytopenic purpura (45), celiac disease (23), juvenile idiopathic arthritis (19), in ammatory bowel disease (46), and rheumatoid arthritis (22) has been reported. The data reported by the current authors have been implied the involvement of the Q63R variation in susceptibility to multiple sclerosis in Iranian patients (18).…”

“…Cannabinoids have been proposed as a promising immunomodulator to reduce the SARS-CoV-2 immunopathology (16). Variations in the cannabinoid CB2 receptor gene (CNR2) could affect intracellular signaling and reduce the ECs function, which has been associated with an unbalanced immune response and increased risk of various in ammatory diseases (17)(18)(19)(20)(21)(22)(23). The CB2-Q63R polymorphism is a missense mutation of the second and third bases at codon 63 of the CNR2 gene, which leads to a Q/R substitution, causing a different polarization state of the protein (24).…”