Genetic Polymorphism of Manganese Superoxide Dismutase is Associated with Childhood Asthma

Genetic Polymorphism of Manganese Superoxide Dismutase is Associated with Childhood Asthma
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DOI:
10.3109/02770901003686472
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发表时间:
2010-06-01
期刊:
影响因子:
1.9
通讯作者:
Wong, Ruey-Hong
Wong, Ruey-Hong
中科院分区:
医学4区
文献类型:
--
作者:
Chou, Tsai-Nung Kuo;Li, Ying-Shiuan;Wong, Ruey-Hong

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目标。细胞对过敏原的防御和活性氧(ROS)暴露在哮喘的发病机制中起着关键作用。CD14是多种细菌产物的受体,如脂多糖(LPS),也是炎症过程的介质。锰超氧化物歧化酶(MnSOD)是一种ROS清除剂,髓过氧化物酶(MPO)可以将过氧化氢转化为次氯酸,因此被认为参与了炎症防御。作者进行了一项基于CD14、MnSOD和MPO基因的病例对照研究,以评估儿童哮喘的易感性。方法:研究方法。应用聚合酶链式反应对116例哮喘患儿和232例健康儿童进行CD14-260、MnSOD-9和MPO-463基因分型。通过问卷调查获得人口统计学特征。过敏原测试使用了台湾常见的空气过敏原。结果。父母文化程度高、哮喘家族史、家中烧香、变应原检测阳性、MnSODVal-Ala/Ala-Ala基因型(匹配相对危险度=2.0;95%可信区间=1.0~4.2)与儿童哮喘显著相关。在这些儿童中,CD14、MnSOD、MPO基因和过敏状态之间的相互作用与哮喘风险显著相关(均p<.001)。此外,携带MnSODVal-Ala/Ala-Ala(对数嗜酸性粒细胞2.66/mm(3),对数血清免疫球蛋白E[IgE]2.48IU/ml)或Val-Val(对数嗜酸粒细胞2.61/mm(3),对数血清总IgE 2.63IU/ml)的特应性患者的嗜酸性粒细胞计数和血清总IgE水平均高于非特应性患者(对数嗜酸性粒细胞2.27/mm(3),对数血清总IgE 1.83IU/ml)。结论。易感MnSOD基因型别可能调节台湾儿童哮喘的发生。
Objective. Cellular defenses against allergens and reactive oxygen species (ROS) exposure are critical in the pathogenesis of asthma. CD14 is a receptor for various bacterial products, such as lipopolysaccharides (LPS), and is also a mediator of inflammatory processes. Manganese superoxide dismutase (MnSOD) is an ROS scavenger, and myeloperoxidase (MPO) can convert hydrogen peroxide into hypochlorous acid; thus, they are considered to be involved in inflammatory defense. The authors conducted a case-control study to evaluate the susceptibility to childhood asthma based on CD14, MnSOD, and MPO genes. Methods. The CD14 - 260, MnSOD - 9, and MPO - 463 genotypes were identified by polymerase chain reactions for 116 asthmatic children and 232 healthy controls. Questionnaires were administered to obtain demographic characteristics. Allergen testing used common Taiwanese aeroallergens. Results. A higher level of parental education, family history of asthma, incense burning at home, allergen-test positive, and the MnSOD Val-Ala/Ala-Ala genotypes (matched relative risk = 2.0; 95% confidence interval = 1.0-4.2) were significantly associated with childhood asthma. Interactions between CD14, MnSOD, MPO genotypes and allergy status were significantly associated with asthma risk in these children (all p < .001). Furthermore, atopic cases with MnSOD Val-Ala/Ala-Ala (log eosinophil 2.66/mm(3), log total serum immunoglobulin E [IgE] 2.48 IU/ml) or Val-Val (log eosinophil 2.61/mm(3), log total serum IgE 2.63 IU/ml) genotypes had elevated eosinophil counts and total serum IgE levels as compared to nonatopic cases with MnSOD Val-Val genotype (log eosinophil 2.27/mm(3), log total serum IgE 1.83 IU/ml). Conclusions. Susceptible MnSOD genotypes might modulate the development of asthma in Taiwanese children.