Can certain genotypes predispose to poor asthma control in children? A pharmacogenetic study of 9 candidate genes in children with difficult asthma.
Can certain genotypes predispose to poor asthma control in children? A pharmacogenetic study of 9 candidate genes in children with difficult asthma.
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DOI：
10.1371/journal.pone.0060592
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shields MD
中科院分区：
文献类型：
--
作者：
Almomani B;Hawwa AF;Millership JS;Heaney L;Douglas I;McElnay JC;Shields MD
我们检验了这样的假设：患有困难性哮喘的患者某些基因型的频率增加，这些基因型使他们容易出现哮喘恶化和哮喘控制不佳。从两个表型组中选出总共 180 名确诊为哮喘的白人儿童；困难组（n = 112）与轻度/中度哮喘组（n = 68）。对所有患者的 9 个候选基因中的 19 个多态性进行了筛查，以评估其与难治性哮喘的关联。结果表明，LTA4H A-9188>G、TNFα G-308>A 和 IL-4Rα A1727>G 多态性与儿科患者难治性哮喘的发生显着相关（分别为 p<0.001、p = 0.019 和 p = 0.037）。单倍型分析还揭示了两种单倍型（ATA单倍型IL-4Rα A1199>C、IL-4Rα T1570>C和IL-4Rα A1727>G和CA单倍型TNFα C-863>A和TNFα G-308>A多态性）与儿童困难哮喘显着相关（p = 0.04和p = 0.018，分别）。该研究揭示了LTA4H、TNFα和IL4-Rα基因中的多个SNP和单倍型，它们构成了儿童难治性哮喘发展的危险因素。特别令人感兴趣的是 LTA4H A-9188>G 多态性，首次报道该多态性与儿童严重哮喘有密切关系。我们的结果表明，筛查具有这种遗传标记的患者可以帮助表征对白三烯修饰药物反应的异质性，从而有助于将这些疗法针对最有可能受益的患者子集。
We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control. A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma. The results indicated that LTA4H A-9188>G, TNFα G-308>A and IL-4Rα A1727>G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p<0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Rα A1199>C, IL-4Rα T1570>C and IL-4Rα A1727>G and CA haplotype of TNFα C-863>A and TNFα G-308>A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively). The study revealed multiple SNPs and haplotypes in LTA4H, TNFα and IL4-Rα genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A-9188>G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit.
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影响因子：
6.7
作者：
Drazen, JM;Silverman, EK;Lee, TH
通讯作者：
Lee, TH
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