title: An interleukin 12 B single nucleotide polymorphism increases IL-12p40 production and is associated with increased disease susceptibility in patients with relapsing-remitting multiple sclerosis.
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.
authors.affiliation: a Faculty of Medicine, Department of Immunology , Zabol University of Medical Sciences , Zabol , Iran.|b Department of Neurology & Neuroscience, Neurosciences Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Javan
authors.affiliation: c Faculty of Medicine, Department of Physiology , Zabol University of Medical Sciences , Zabol , Iran.
authors.forename: Sarieh
authors.initials: S
authors.lastname: Shahraki
authors.affiliation: a Faculty of Medicine, Department of Immunology , Zabol University of Medical Sciences , Zabol , Iran.
authors.forename: Amin
authors.initials: A
authors.lastname: Safa
authors.affiliation: d Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|e Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zamani
authors.affiliation: f Faculty of Medicine, Student Research Committee, Medical Genetics Research Center , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Salmaninejad
authors.affiliation: d Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Aslani
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004185:Disability Evaluation; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D013223:Statistics as Topic
chemical_list: C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger
keywords: IL12B; IL23R; Multiple sclerosis; SNP; gene expression