title: Impact of interleukin 13 (IL13) genetic polymorphism Arg130Gln on total serum immunoglobulin (IgE) levels and interferon (IFN)-γ gene expression.
abstract: This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)-4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Gln576Arg, in the control of serum total and antigen-specific immunoglobulin (Ig)E levels. Furthermore, we analysed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response [IL-4, IL-13, interferon (IFN)-γ, IL-8 and IL-10]. Total and antigen-specific IgE levels in serum and gene expression of selected cytokines in peripheral blood were measured in 386 children aged 1-8 years. TaqMan allelic discrimination, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphisms (RFLP) methods validated by sequencing were used for genotyping. All genotypes for children with total and antigen-specific IgE levels in the normal range were in Hardy-Weinberg equilibrium. Gene expression analyses were carried out using TaqMan gene expression assays. We found elevated total IgE levels in carriers of IL13 Arg130Gln variant allele [odds ratio (OR) = 1·84; 95% confidence interval (CI) = 1·16-2·93]. This effect was more apparent for boys (OR = 2·31; 95% CI = 1·25-4·28). However, no significant association was observed for the other four variants examined. We found up-regulation of IFN-γ in children with elevated serum total IgE levels carrying the Arg130 allele (P = 0·005). No differences were found for IL4, IL8 or IL10, while IL13 gene expression was under the detection limit. IL13 Arg130Gln genotypes can play a role in genetic susceptibility to allergy via regulation of serum total IgE levels and affecting IFN-γ gene expression.
authors.affiliation: Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.|Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: B
authors.identifier: 0000-0002-4906-5652
authors.initials: B
authors.lastname: Smolkova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Tulinska
authors.affiliation: Faculty of Public Health, Slovak Medical University, Bratislava, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Palkovicova Murinova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: V
authors.initials: V
authors.lastname: Buocikova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: A
authors.initials: A
authors.lastname: Liskova
authors.affiliation: Faculty of Public Health, Slovak Medical University, Bratislava, Slovakia.
authors.forename: K
authors.initials: K
authors.lastname: Rausova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Kuricova
authors.affiliation: Faculty of Public Health, Slovak Medical University, Bratislava, Slovakia.
authors.forename: H
authors.initials: H
authors.lastname: Patayova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Sustrova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: E
authors.initials: E
authors.lastname: Neubauerova Svorcova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: S
authors.initials: S
authors.lastname: Ilavska
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Szabova
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: T
authors.initials: T
authors.lastname: Nemessanyi
authors.affiliation: Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
authors.forename: E
authors.initials: E
authors.lastname: Jahnova
authors.affiliation: Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Kjeller, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Dusinska
authors.affiliation: Faculty of Medicine, 1st Pediatric Department, Comenius University, Bratislava, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Ciznar
authors.affiliation: College of Public Health, University of Iowa, Iowa City, IA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Fuortes
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D003062:Codon; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics*; D018793:Interleukin-13 / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics
chemical_list: D003062:Codon; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma
keywords: allergy; cytokines; molecular biology