Cannabinoid CB2 Receptor Functional Variation (Q63R) Is Associated with Multiple Sclerosis in Iranian Subjects
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Cannabinoid CB2 Receptor Functional Variation (Q63R) Is Associated with Multiple Sclerosis in Iranian Subjects Alireza Tahamtan 1,2 & Shahrzad Rezaiy 3 & Saeed Samadizadeh 2 & Abdolvahab Moradi 2 & Alijan Tabarraei 2 & Naeme Javid 2 & Morteza Oladnabi 4 & Mohammad Hosein Naeimi 5 Received: 21 January 2019 / Accepted: 1 August 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract The cannabinoid system has been identified as a critical endogenous regulator of immune homeostasis through immunomodulatory actions. This system is one of the main regulatory systems of the central nervous system (CNS). Variations in the cannabinoid CB2 receptor gene (CNR2) could affect intracellular signaling and reduce system function, which has been associated with an unbalanced immune response and increased risk of a variety of autoimmune inflammatory disorders. The present study investigated the relationship between CNR2 rs35761398 (Q63R) functional variation and multiple sclerosis (MS). A total of 100 Iranian MS patients and 100 healthy controls were enrolled in the study and genotyped through TaqMan assay. The codominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software. A significant genetic association was observed between Q63R polymorphism and MS. The dominant model was accepted as the best inheritance model to fit the data (OR 2.70, 95% CI 1.47–4.97, p = 0.001). The data implied the involvement of the CNR2 gene in susceptibility to MS in Iranian patients. Keywords Cannabinoid receptor type 2 . Multiple sclerosis . Single-nucleotide polymorphism . CNR2 . Q63R . Iran
Introduction Cannabinoids are a group of endogenous and exogenous compounds that function through the activation of their respective receptors, CB1 and CB2 (Reggio 2010). In addition to psychoactive functions, the cannabinoid system has the ability to alter immune function, drawing significant attention (Nagarkatti et al. 2009). Cannabinoid signaling interacts mainly with the immune system and regulates the development, migration, proliferation, and effector functions of immune cells, representing the key component of the system for
* Alireza Tahamtan [email protected]; [email protected] 1
Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran
2
Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
3
Islamic Azad University of Mashhad, Mashhad, Iran
4
Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
5
Department of Neurology, Sayyad Hospital, Golestan University of Medical Sciences, Gorgan, Iran
immune function modulation and autoimmunity (Witkamp and Meijerink 2014). Studies have verified that genetic variants in the cannabinoid system affect immune functions and have an impact on disease severity (Tahamtan et al. 2018). The single-nucleotide polymorphism (SNP) rs35761398 (Q63R) in the CNR2 gene, which encodes the cannabinoid receptor type 2 (
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