Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology & Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Allergy. 2011 Dec;66(12):1546-52. doi: 10.1111/j.1398-9995.2011.02701.x. Epub 2011 Sep 29.
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.
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).
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).
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.
先前的研究发现，T2206C FCER2 变异与接受吸入性皮质类固醇（ICS）治疗的儿童的 IgE 水平、加重率和 FCER2 表达降低有关。这一发现尚未得到复制。我们试图复制 FCER2 基因与哮喘儿童加重之间的关联。此外，我们还测试了 T2206C 变异是否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。
使用接受 ICS 治疗的哮喘儿童的两个人群的数据（Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects study，n=386 和 BREATHE 研究，n=939），探讨 T2206C 变异对哮喘加重（急诊就诊或住院）、症状评分和药物使用的影响。
T2206C 变异与两个队列中与哮喘相关的住院风险增加相关（OR：1.91，95%CI：1.08-3.40），与之前发表的结果进行荟萃分析具有高度显著性（OR：2.38，95%CI：1.47-3.85，P=0.0004）。FCER2 变异也与哮喘控制问卷（Asthma Control Questionnaire）测量的未控制哮喘风险增加相关（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）。
在接受类固醇治疗的哮喘患者中，FCER2 T2206C 变异与哮喘相关住院之间的关联似乎是可靠的，也可能与 ICS 疗效缺乏的其他指标相关，如哮喘症状和需要更高剂量的 ICS。我们的研究结果表明，FCER2 T2206C 变异可能是类固醇难治性患者的一种有用的药物遗传学预测因子。
