吸入性糖皮质激素治疗儿童哮喘的反应性：CRHR1基因rs242941多态性的作用
Responsiveness of Inhaled Corticosteroid Treatment in Children with Asthma: The Role of rs242941 Polymorphism of CRHR1 Gene.
作者信息
Nguyen-Thi-Bich Hanh, Nguyen-Thi-Dieu Thuy, Nguyen-Ngoc-Quynh Le, Le-Thi-Minh Huong, Duong-Quy Sy
机构信息
Department of Immuno-Allergology and Asthma, National Children's Hospital, Hanoi, Vietnam.
Department of Pediatrics, Hanoi Medical University, Hanoi, Vietnam.
出版信息
Pulm Ther. 2023 Mar;9(1):127-137. doi: 10.1007/s41030-022-00205-9. Epub 2022 Dec 2.
INTRODUCTION
Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness.
METHODS
This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1 s (FEV) after treatment versus at inclusion.
RESULTS
In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters.
CONCLUSION
TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV.
引言
吸入性糖皮质激素（ICS）是治疗哮喘最广泛使用且有效的药物。然而，一些患者对ICS无反应，这可能归因于多种遗传因素。因此，了解参与ICS反应的遗传因素有助于医生为特定患者制定个性化的治疗决策和行动计划。本研究旨在分析哮喘儿童促肾上腺皮质激素释放激素受体1（CRHR1）基因型的特征以及CRHR1基因rs242941多态性与ICS反应性之间的相关性。
方法
这项前瞻性研究纳入了哮喘控制不佳的儿童，评估他们的嗜酸性粒细胞计数、免疫球蛋白E（IgE）浓度、肺功能以及呼出气一氧化氮分数浓度（FENO），并进行CRHR1多态性测序。通过哮喘控制测试（ACT）评估哮喘控制水平；通过测量治疗后与纳入时ACT和第1秒用力呼气容积（FEV）的变化来评估ICS治疗哮喘的反应性。
结果
总共对107例患者的rs242941位点进行了CRHR1分析。其中，86例（80.3%）为纯合野生型GG，20例（18.7%）为杂合GT基因型，1例（1.0%）为纯合变异型TT。有特应性个人和家族史的儿童更可能具有GT和TT基因型。rs242941位点CRHR1基因的GG、GT和TT基因型三组哮喘儿童的哮喘严重程度相似。GG和GT基因型哮喘儿童的FENO水平、总IgE浓度和嗜酸性粒细胞计数无显著差异。纯合变异型TT基因型患者的FENO水平较高。rs242941位点的CRHR1多态性与通过哮喘控制测试评估的哮喘控制和肺功能参数之间无相关性。
结论
CRHR1基因rs242941的TT基因型并不常见。具有CRHR1基因rs242941多态性的哮喘儿童的临床和功能特征仍然高度相似。rs242941多态性与ACT或FEV之间无相关性。
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