Wang T-N, Chiang W, Tseng H-I, Chu Y-T, Chen W-Y, Shih N-H, Ko Y-C
Faculty of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
Allergy. 2007 Oct;62(10):1125-30. doi: 10.1111/j.1398-9995.2007.01485.x.
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.
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.
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.
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.
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.
哮喘是一种复杂的疾病，已知受遗传和环境因素相互作用的影响。人嗜酸性粒细胞趋化因子1（Eotaxin 1）和CC趋化因子受体3（CCR3）吸引嗜酸性粒细胞和Th2淋巴细胞迁移至炎症病灶，这可能是过敏和哮喘的关键机制。
我们推测Eotaxin1基因Ala23Thr和A-384G以及CCR3基因T51C多态性与血浆嗜酸性粒细胞趋化因子水平相关，并使个体易患哮喘发病机制。
在台湾南部招募了178名5至12岁的住院哮喘儿童和277名社区对照。采集全血样本和问卷。在本研究中，我们探讨了Eotaxin 1和CCR3基因对哮喘、血浆免疫球蛋白E（IgE）和嗜酸性粒细胞趋化因子1水平的遗传影响。
与Ala23Ala基因型受试者相比，Eotaxin 1基因的Ala23Thr多态性对哮喘具有显著的保护作用（比值比[AOR]=0.58，95%可信区间[CI]=0.37-0.92）。我们证明，Ala23Ala受试者的平均嗜酸性粒细胞趋化因子1浓度显著高于Thr23Thr受试者（P=0.005）或Ala23Thr受试者（P=0.07），呈现基因剂量依赖性关系。但是，我们观察到Eotaxin 1基因的A-384G多态性和CCR3基因的T51C多态性与哮喘无关。
本研究结果提供了有力证据，表明嗜酸性粒细胞趋化因子1 Thr23Thr纯合子对哮喘具有保护作用，并显著降低台湾哮喘患者的血浆嗜酸性粒细胞趋化因子1浓度。
