The polymorphisms of Eotaxin 1 and CCR3
genes influence on serum IgE, Eotaxin levels
and mild asthmatic children in Taiwan
T.-N. Wang1, W. Chiang2,3, H.-I. Tseng4, Y.-T. Chu4, W.-Y. Chen4, N.-H. Shih2, Y.-C. Ko5,6
1Faculty of Public Health, Kaohsiung Medical University; 2Department of Laboratory Medicine, Kaohsiung Medical University Hospital; 3School of Medicine, Kaohsiung Medical University;
4Department of Pediatrics, Kaohsiung Medical University; 5Department of Public Health, Faculty of Medicine, Kaohsiung Medical University; 6Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Kaohsiung, Taiwan
Asthma is a common disease in children that is caused by acute and chronic inflammation in the airways. Asthma evokes chronic inflammatory reactions mediated when a number of chemokines are produced. Eotaxin 1 is a member of the CC chemokine family. It can recruit
circulating eosinophils, basophils and Th2-lymphocytes to the inflammatory foci from the blood stream. CCR3 is a G protein-coupled receptor of Eotaxin 1 and is expressed in eosinophils and Th2 lymphocytes (1). These chemotaxis effects of Eotaxin 1 are mediated via CCR3
and could represent a key mechanism in allergy and asthma (1–5). The human Eotaxin 1 and CCR3 genes are located on chromosome 17q21.1-q21 with three exons (_8 kb) (6, 7) and chromosome 3p21.3 (8) respectively. The expression of Eotaxin 1 mRNA and protein was found to be increased in the bronchial epithelium and endothelial cells of the airways of atopic asthmatics. Furthermore, the elevation of Eotaxin 1 levels was proportional to eosinophil infiltration and bronchial hyper-reactivity (2, 9) and associated with impaired lung function of the asthmatics (10). Stellato et al. (11) detected expression of CCR3 in eosinophils and airway
epitheliums from asthmatic patients. An animal study showed that CCR3 disruption significantly curtails eosinophil recruitment to the lung after allergen challenge
(12). Ma et al. (13) found CCR3)/) mice repeatedly sensitized by epicutaneous application of
ovalbumin failed to attract eosinophils to the skin. Therefore, CCR3 is critical for eosinophil recruitment to both the skin and the lung and in the development of air way hyper-responsiveness. In this study, Ala23Thr and A-384G polymorphisms of Eotaxin 1 gene and T51C polymorphism of CCR3 gene have been tested. This
genetic association study was conducted to address inherited predisposition to Eotaxin 1 and CCR3 gene in Taiwan and their effects on plasma IgE, Eotaxin 1 levels and asthma. 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.