Tantisira Kelan G, Silverman Eric S, Mariani Thomas J, Xu Jingsong, Richter Brent G, Klanderman Barbara J, Litonjua Augusto A, Lazarus Ross, Rosenwasser Lanny J, Fuhlbrigge Anne L, Weiss Scott T
Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Allergy Clin Immunol. 2007 Dec;120(6):1285-91. doi: 10.1016/j.jaci.2007.09.005. Epub 2007 Nov 5.
Although inhaled corticosteroids (ICSs) generally protect against severe exacerbations in asthma, they may result in elevated IgE levels, which are associated with exacerbations.
To determine whether variation in the low-affinity IgE receptor gene, FCER2, is associated with severe exacerbations defined as emergency department visits and/or hospitalizations in patients with asthma on ICSs.
We resequenced, then genotyped 10 FCER2 single nucleotide polymorphisms (SNPs) in 311 children randomized to inhaled budesonide as part of the Childhood Asthma Management Program. We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial. We also evaluated differences in cellular expression of the novel FCER2 SNP, T2206C.
In white subjects, 3 FCER2 SNPs were significantly associated (P < .05) with elevated 4-year IgE level; each was also associated with increased severe exacerbations. Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children (hazard ratio, 3.95; 95% CI, 1.64-9.51; and hazard ratio, 3.08; 95% CI, 1.00-9.47), despite ICS use. Interaction models supported a true gene-environment effect in white subjects (interaction P = .004). T2206C was also associated with decreased FCER2 expression (P = .02).
FCER2 predicts the likelihood of treatment protocol success in asthma. The associations of T2206C with IgE level, severe exacerbations, and FCER2 expression may provide a mechanistic basis for the observed findings.
Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma.
尽管吸入性糖皮质激素（ICSs）通常可预防哮喘严重发作，但它们可能导致IgE水平升高，而IgE水平升高与发作有关。
确定低亲和力IgE受体基因FCER2的变异是否与ICS治疗的哮喘患者因急诊就诊和/或住院定义的严重发作相关。
我们对参与儿童哮喘管理项目且随机接受吸入布地奈德治疗的311名儿童的10个FCER2单核苷酸多态性（SNP）进行了重测序，然后进行基因分型。我们评估了FCER2变异与4年临床试验期间IgE水平及严重发作的有无之间的关联。我们还评估了新型FCER2 SNP T2206C的细胞表达差异。
在白人受试者中，3个FCER2 SNP与4年IgE水平升高显著相关（P <.05）；每个SNP也与严重发作增加相关。最终多变量模型显示，T2206C与白人和非裔美国儿童的严重发作均有关联（风险比，3.95；95%CI，1.64 - 9.51；以及风险比，3.08；95%CI，1.00 - 9.47），尽管使用了ICS。交互作用模型支持白人受试者中存在真正的基因 - 环境效应（交互作用P =.004）。T2206C也与FCER2表达降低相关（P =.02）。
FCER2可预测哮喘治疗方案成功的可能性。T2206C与IgE水平、严重发作及FCER2表达之间的关联可能为观察到的结果提供机制基础。
FCER2的基因变异可能有助于形成哮喘患者ICS反应的预后模型。
