ABSTRACT
BACKGROUND: Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The human Eotaxin 1 and CCR3 attract eosinophils and Th2-lymphocytes to migrate to the inflammatory foci that could represent a key mechanism in allergy and asthma. OBJECTIVE: We hypothesized that Eotaxin1 gene Ala23Thr and A-384 G, and CCR3 gene T51C polymorphisms are associated with plasma Eotaxin levels and predispose individuals to asthma pathogenesis. METHODS: One hundred seventy-eight hospital-based asthmatic children and 277 community-based controls aged from 5 to 12 years were recruited in southern Taiwan. Whole blood samples and questionnaires were collected. In this study, we addressed genetic effects of Eotaxin 1 and CCR3 genes on asthma, plasma IgE and Eotaxin 1 levels. RESULTS: In comparison with subjects with Ala23Ala genotype, Ala23Thr polymorphism of the Eotaxin 1 gene showed a significant protective effect on asthma (AOR = 0.58, 95% CI = 0.37-0.92). We demonstrated that the mean Eotaxin 1 concentration was significantly higher in subjects with Ala23Ala than in subjects with Thr23Thr (P = 0.005) or Ala23Thr (P = 0.07), which showed a gene-dose dependent relationship. But, we observed that the A-384G polymorphism of Eotaxin 1 gene and T51C polymorphism of CCR3 gene are not associated with asthma. CONCLUSION: This study finding provide a strong evidence that Eotaxin 1 Thr23Thr homozygote has a protective effect on asthma and significantly decreases plasma Eotaxin 1 concentrations in asthmatics in Taiwan.
Subject(s)
Asthma/genetics , Asthma/immunology , Chemokine CCL11/blood , Chemokine CCL11/genetics , Immunoglobulin E/blood , Polymorphism, Genetic/genetics , Receptors, CCR3/genetics , Child , Child, Preschool , DNA/blood , DNA/isolation & purification , Eosinophils/immunology , Eosinophils/metabolism , Female , Gene Frequency/immunology , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Polymorphism, Genetic/immunology , Polymorphism, Restriction Fragment Length/genetics , Polymorphism, Restriction Fragment Length/immunology , Polymorphism, Single Nucleotide/genetics , Polymorphism, Single Nucleotide/immunology , Receptors, CCR3/metabolism , Reference Values , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , TaiwanABSTRACT
BACKGROUND: Asthma is a multi-factorial disorder caused by complex interactions between genetic and environmental factors. IFN-gamma and IFN regulatory factor 1 (IRF-1) affect Th1/Th2 cytokine balance, and influence the differentiation of Th2 cells, which influence the development of asthma. OBJECTIVE: This study investigated CA repeats polymorphism of the IFN-gamma gene and GT repeats polymorphism of the IRF-1 gene, which may predispose individuals to asthma pathogenesis. METHODS: In the present study, we used the transmission/disequilibrium test (TDT) to investigate the relationship between asthma and the IFN-gamma and IRF-1 polymorphisms by studying 348 subjects composed of 232 parents and 116 asthmatic children. RESULTS: For global TDT test, IFN-gamma CA repeats and IRF-1 GT repeat polymorphisms showed a significant association with asthma in children (P=0.009 and 0.017, respectively). We demonstrated that 13 CA repeats (138 bp) of IFN-gamma gene and 11 GT repeats (306 bp) of IRF-1 gene are significantly preferentially transmitted to asthmatic children (T/NT=89/61, chi2=8.43, P<0.005 and T/NT=75/49, chi2=8.18, P<0.005, respectively). The offspring will have an increased risk of asthma when their parents transmit IFN-gamma 13 CA repeats (OR=1.83, P=0.009) and IRF1 11 GT repeats (OR=1.88, P=0.007) to them. But we observed that the IFN-gamma and IRF-1 polymorphisms are not associated with IgE concentrations. CONCLUSION: These findings provide strong evidence of which IFN-gamma CA repeat and IRF-1 GT repeat polymorphisms influence the risk of asthma for children in Taiwan.
Subject(s)
Asthma/genetics , Interferon Regulatory Factor-1/genetics , Interferon-gamma/genetics , Polymorphism, Genetic/genetics , Adult , Asthma/blood , Child , Family Health , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Humans , Immunoglobulin E/blood , Linkage Disequilibrium/genetics , Male , Phenotype , TaiwanABSTRACT
Asthma occurs in genetically susceptible individuals in the presence of environmental factors. The interleukin-9 (IL-9) gene, one of the cytokine genes located on chromosome 5q31, plays an important role in the development of asthmatic syndrome by enhancing both T-cell and mast-cell function. This study investigated GT repeat polymorphism of the IL-9 gene and the gene-environment interactions, which may predispose individuals to asthma and atopy pathogenesis. In this study, we used the transmission/disequilibrium test (TDT) to investigate the relationship between asthma and the IL-9 gene by studying 123 parent-offspring trios and 91 siblings. For allele-specific TDT chi-squared test, allele 122 of the IL-9 gene showed significant association with asthmatics with specific IgE against house dust (HD) (P = 0.038). The additions of covariates to TDT to conduct the synergistic effects between the IL-9 gene and environmental factors into account were estimated by conditional logistic regression models. The odds ratio for transmission of allele 122 of the IL-9 gene was 1.23 (P = 0.28) for all asthmatic probands. There was slight increased interaction effect on asthma between transmission of allele 122 of IL-9 gene to offspring and who were exposed to the fur of pets (OR = 3.33, P = 0.047). We also detected elevated odds of transmission of allele 122 to atopic asthmatic probands (OR = 2.08, P = 0.03) and offspring with very high levels of serum IgE (> or = 800 IU mL(-1)). In conclusion, this study has found that the IL-9 gene was slightly associated with asthmatics who have positive specific IgE against Der p (or Der f) and house dust, when information on environmental factors was incorporated as effect modifiers.
