FCER2 T2206C variant associated with chronic symptoms and exacerbations in steroid-treated asthmatic children
FCER2 T2206C variant associated with chronic symptoms and exacerbations in steroid-treated asthmatic children
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DOI：
10.1111/j.1398-9995.2011.02701.x
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发表时间：
2011-12-01
期刊：
影响因子：
12.4
通讯作者：
Palmer, C. N. A.
中科院分区：
文献类型：
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作者：
Koster, E. S.;Maitland-van der Zee, A-H.;Palmer, C. N. A.
背景资料：先前发现T2206 C FCER 2变异体与参与临床试验的吸入性皮质类固醇（ICS）儿童的IgE水平、加重率和FCER 2表达降低相关。这一发现尚未得到证实。我们试图复制FCER 2基因与哮喘儿童急性发作之间的关联。此外，我们还检验了T2206 C变异可能与其他类固醇抵抗标志物（如哮喘症状评分和哮喘药物使用）相关的假设。使用来自使用ICS的两个哮喘儿童人群的数据，探索了（急诊科就诊或住院）、症状评分和药物使用情况：儿童哮喘药物的药物遗传学：抗炎作用药物研究（n = 386）和BREATHE研究（n = 939）。结果：T2206 C变异与两个队列中哮喘相关的医院就诊风险增加相关（OR：1.91，95%CI：1.08-3.40），与先前发表的结果的荟萃分析具有高度显著性（OR：2.38，95%CI：1.47-3.85，P = 0.0004）。FCER 2变异体还与哮喘控制问卷测量的不受控制的哮喘风险增加相关（OR：2.64，95%CI：1.00-6.98），并与每日类固醇剂量增加相关（OR：2.46，95%CI：1.38-4.39）。FCER 2 T2206 C变异体与激素依赖性哮喘患者哮喘相关住院治疗之间的关系治疗的哮喘表现出稳健性，并且还可能与缺乏ICS功效的其他指标相关，例如哮喘症状和需要更高的ICS日剂量。我们的研究结果表明，FCER 2 T2206 C变异可能是一个有用的类固醇难治性患者的药物遗传学预测。
Background: The T2206C FCER2 variant was found previously to be associated with IgE levels, exacerbation rates and decreased FCER2 expression in children on inhaled corticosteroids (ICS) participating in a clinical trial. This finding has not been replicated. We sought to replicate the association between the FCER2 gene and exacerbations in children with asthma. In addition, we tested the hypothesis that the T2206C variant may be associated with other markers of steroid resistance such as asthma symptom scores and asthma medication use.Methods: The influence of the T2206C variant on asthma exacerbations (emergency department visits or hospitalization), symptoms scores and medication use was explored using data from two populations of asthmatic children using ICS: Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects study (n = 386) and BREATHE study (n = 939).Results: The T2206C variant was associated with increased risk of asthma-related hospital visits in both cohorts (OR: 1.91, 95%CI: 1.08-3.40), and meta-analysis with previously published results was highly significant (OR: 2.38, 95%CI: 1.47-3.85, P = 0.0004). The FCER2 variant was also associated with increased risk of uncontrolled asthma measured by Asthma Control Questionnaire (OR: 2.64, 95%CI: 1.00-6.98) and was associated with increased daily steroid dose (OR: 2.46, 95%CI: 1.38-4.39).Conclusion: The association between the FCER2 T2206C variant and asthma-related hospitalizations in steroid-treated asthma appears robust and may also be associated with other indicators of lack of ICS efficacy such as asthma symptoms and a requirement for higher daily doses of ICS. Our results suggest that the FCER2 T2206C variant might be a useful pharmacogenetic predictor of steroid refractory patients.