Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children (original) (raw)
Related papers
American Journal of Respiratory Cell and Molecular Biology, 2001
Asthma and atopy are related conditions that may share similar genetic susceptibility. Linkage studies have identified a region on chromosome 5q that contains biologic candidates for both asthma and atopy phenotypes, including several proinflammatory cytokines. Interleukin (IL)-13, one of the candidate genes in the region, is directly involved in the regulation of immunoglobulin E and has been associated with both asthma and atopy. We sought to identify new polymorphisms in the IL-13 gene, and evaluated the involvement of a subset of these variants in asthma and atopy in a case-control study using probands and spouses from a Dutch asthma family study. IL-13 was sequenced in 20 probands and 20 unaffected spouses, and 10 polymorphisms were identified, four novel and six previously reported. Three single nucleotide (nt) polymorphisms (SNPs) were detected in the 5 Ј-promoter region, two in intron 1, and five in exon 4. Only one of the exon 4 SNPs resulted in an amino-acid change (Arg130Gln). We analyzed three SNPs in IL-13 in an extended group of 184 probands and their spouses: one in the promoter region (Ϫ 1111), the Arg130Gln (nt position 4257), and a 3 Ј untranslated region SNP (nt position 4738). The most significant associations were observed to asthma (P ϭ 0.005), bronchial hyperresponsiveness (P ϭ 0.003), and skin-test responsiveness (P ϭ 0.03) with the Ϫ 1111 promoter. These results provide evidence that variation in the IL-13 gene is involved in the pathogenesis of asthma and atopy. Further investigation is required to determine which specific alleles or combination of alleles contribute to these phenotypes, and the possible downstream effects of the resulting change in IL-13 levels or activity.
2017
This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)24/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)-g, 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) 5 1Á84; 95% confidence interval (CI) 5 1Á16-2Á93]. This effect was more apparent for boys (OR 5 2Á31; 95% CI 5 1Á25-4Á28). However, no significant association was observed for the other four variants examined. We found up-regulation of IFN-g in children with elevated serum total IgE levels carrying the Arg130 allele (P 5 0Á005). 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-g gene expression.
Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms
Revista Portuguesa de Pneumologia (English Edition)
Background: Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. Purpose: To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry. Methods: 192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays. Results: Comparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR)-1.96; 95% CI-1.18 to 3.25; p = 0.010). The association sustains for allergic asthma (OR-2.17; 95% CI-1.23 to 3.80; p = 0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR-0.55, 95% CI-0.33 to 0.94, p = 0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR-0.20; 95% CI of 0.07 to 0.56; p = 0.002). A similar association was found for IL13 rs20541 GG genotype (OR-0.48; 95% CI of 0.25 to 0.93; p = 0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism' analyzed.
Interleukin 13 and Interleukin 4 Receptor-α Polymorphisms in Rhinitis and Asthma
International Archives of Allergy and Immunology, 2010
consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C-1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. Conclusion: IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma.
Interleukin 3 ( IL3 ) polymorphisms associated with decreased risk of asthma and atopy
Journal of Human Genetics, 2004
Cytokines, having central functions in immunological and inflammatory process, are always expected to play important roles in the pathogenesis of various diseases, such as asthma. Genetic polymorphisms of those cytokine and cytokine receptor genes are the focus of genetic association studies. In an effort to identify gene(s) whose variant(s) are involved in the development of asthma, we examined the genetic effects of 19 single nucleotide polymorphisms in eight cytokine and cytokine receptor genes, including IL1A, IL1B, IL2, IL3, IL4, IL8, IL10, and IL5RA, on asthma and atopy. Nineteen single nucleotide polymorphisms in eight cytokine and cytokine receptor genes were genotyped using the single-base extension method in a Korean asthma cohort (n=723). Logistic regression and multiple regressions were used for statistical analyses controlling for smoking, age, and gender as covariables. Genetic association analysis of polymorphisms revealed that one exonic (exon 1), IL3+79T>C (Ser27Pro), showed significant association with the risk of asthma and atopy. The Pro allele had shown dominant and protective effects on development of asthma in nonatopic subjects (P=0.002) and also showed significant association with the risk of atopy in normal control subjects (P=0.007). This information about the genetic association of important genes with asthma might provide valuable insights into strategies for the pathogenesis of asthma and atopy.
American Journal of Respiratory and Critical Care Medicine, 2000
Polymorphisms in the TNF-␣ (A-308G), IL-4 (C-589T), and Fc RI  (E237G) genes have been associated with asthma and related phenotypes. To determine the predictive value of these polymorphisms we have assessed their relative risk (RR) for the development of atopy, asthma, and rhinitis in a high-risk infant population that is being followed longitudinally from birth. DNA was extracted and genotyped for 373 infants and 572 parents for each polymorphism. Phenotypic data were collected for atopy and allergic diseases in the infants at 12 mo of age. The prevalence of these phenotypes in the 281 white infants was compared in each genotypic group. There were no differences in the prevalence of any phenotype between genotypes of the TNF-␣ and Fc RI  polymorphisms. However, we found that the IL4-589*T allele was associated with "probable" asthma (RR ϭ 4.1) and that homozygotes for the IL4-589*T allele had an increased risk for the development of rhinitis (RR ϭ 2.4). Using the transmission disequilibrium test, an association of IL4-589*T with atopy was found. We conclude that IL-4-589*T, but not TNF-␣-308*2 or Fc RI  *G, is a risk factor for the development of atopy, asthma, and rhinitis by 12 mo of age.
Advances in Medical Sciences, 2016
Interleukin 4 (IL4), interleukin 4 receptor (IL4R) and interleukin 13 (IL13) play a key role in the pathogenesis of allergy and asthma development. IL4 and IL13 strongly influence bronchial hyperreactivity in response to allergen, airway remodeling, airway inflammation and airway smooth muscle proliferation. Both IL4 and IL13 exert biologic effect via interleukin 4 receptor. The aim of this study was to evaluate the impact of the polymorphisms within interleukin 4 (rs2243250, rs2227284), interleukin 4 receptor a chain (rs1805010, rs1805011) and interleukin 13 (rs20541) genes on the incidence of allergic phenotype in Polish pediatric population. Material/methods: We compared 177 asthmatic pediatric patients with 194 healthy children. Five polymorphisms within IL4, IL13 and IL4Ra genes were analyzed. Genotypes of four polymorphisms (rs2243250, rs2227284, rs1805011, rs20541) were assigned by TaqMan SNP Genotyping Assays (Applied Biosystems), whereas rs18050100 polymorphism was established using PCR-RFLP method. Results: We observed an association of rs1805011 polymorphism of IL4Ra gene with allergy (p = 0.021), mild asthma (p = 0.00005) and atopic dermatitis (p = 0.0056). Significant correlation was found between rs20541 in IL-13 gene and the positive skin prick test results (p = 0.029), along with rs2243250 polymorphism with clinical atopy (p = 0.033) and rs2227284 with total IgE levels (p = 0.00047). No associations were found for rs1805010. Conclusions: Our results indicate that rs1805011 polymorphism of IL4Ra gene seems to influence allergy risk, especially mild asthma and atopic dermatitis predisposition in Polish children. Subgroup analysis of three other SNPs revealed possible influence on allergy development.