Mohammad Reza Javan1,2, Sarieh Shahraki3, Amin Safa1, Mohammad Reza Zamani4,5, Arash Salmaninejad6, Saeed Aslani4. 1. a Faculty of Medicine, Department of Immunology , Zabol University of Medical Sciences , Zabol , Iran. 2. b Department of Neurology & Neuroscience, Neurosciences Research Center , Tabriz University of Medical Sciences , Tabriz , Iran. 3. c Faculty of Medicine, Department of Physiology , Zabol University of Medical Sciences , Zabol , Iran. 4. d Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran. 5. e Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran. 6. f Faculty of Medicine, Student Research Committee, Medical Genetics Research Center , Mashhad University of Medical Sciences , Mashhad , Iran.
Abstract
BACKGROUND: Through mounting genetic investigations, it has been established that IL12B and IL23R gene single nucleotide polymorphisms have significant associations with autoimmune diseases including inflammatory bowel disease, psoriasis, and ankylosing spondylitis. IL-12/IL-23 pathway plays a pivotal role in etiopathogenesis of multiple sclerosis (MS), suggested by studies both in patients and animal models. METHODS: In a case-control study, 145 MS patients and 200 healthy subjects were genotyped for polymorphisms in IL12B and IL23R genes using Real-Time PCR allelic discrimination approach. Additionally, quantitative analysis of mRNA expression of IL12B in Peripheral Blood Mononuclear Cells from patients and controls was conducted through Real-Time PCR using the TaqMan Gene Expression Assay. RESULTS: The rs6887695 single-nucleotide polymorphism (SNP) in IL12B gene showed an association with susceptibility to MS. GG genotype of this variation was more frequent in patients. mRNA expression of IL12B was upregulated in patients. Expression of IL12B mRNA in both MS patients collectively and those with GG genotype for rs6887695 SNP correlated negatively with onset age of MS patients. CONCLUSIONS: The GG genotype of rs6887695 SNP in IL12B gene plays a role in etiopathogenesis of MS.
BACKGROUND: Through mounting genetic investigations, it has been established that IL12B and IL23R gene single nucleotide polymorphisms have significant associations with autoimmune diseases including inflammatory bowel disease, psoriasis, and ankylosing spondylitis. IL-12/IL-23 pathway plays a pivotal role in etiopathogenesis of multiple sclerosis (MS), suggested by studies both in patients and animal models. METHODS: In a case-control study, 145 MSpatients and 200 healthy subjects were genotyped for polymorphisms in IL12B and IL23R genes using Real-Time PCR allelic discrimination approach. Additionally, quantitative analysis of mRNA expression of IL12B in Peripheral Blood Mononuclear Cells from patients and controls was conducted through Real-Time PCR using the TaqMan Gene Expression Assay. RESULTS: The rs6887695 single-nucleotide polymorphism (SNP) in IL12B gene showed an association with susceptibility to MS. GG genotype of this variation was more frequent in patients. mRNA expression of IL12B was upregulated in patients. Expression of IL12B mRNA in both MSpatients collectively and those with GG genotype for rs6887695 SNP correlated negatively with onset age of MSpatients. CONCLUSIONS: The GG genotype of rs6887695 SNP in IL12B gene plays a role in etiopathogenesis of MS.
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