title: Polymorphisms of genes encoding interleukin-4 and its receptor in Iranian patients with juvenile idiopathic arthritis.
abstract: As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value = 0.03, and P value = 0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses.
authors.affiliation: Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Ziaee
authors.affiliation: Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.
authors.forename: Arezou
authors.initials: A
authors.lastname: Rezaei
authors.affiliation: Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.|Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Harsini
authors.affiliation: Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Maddah
authors.affiliation: Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.|Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Zoghi
authors.affiliation: Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sadr
authors.affiliation: Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Moradinejad
authors.affiliation: Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, Tehran, 14194, Iran. rezaei_nima@tums.ac.ir.|Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. rezaei_nima@tums.ac.ir.|Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir.
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
mesh_terms: D000293:Adolescent; D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D007492:Iran; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C508598:IL4 protein, human; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D015847:Interleukin-4
keywords: Interleukin-4; Juvenile idiopathic arthritis; Single nucleotide polymorphism