Department of Clinical Pathology & Immunology, Ain Shams University, Cairo, Egypt.
Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Int Forum Allergy Rhinol. 2020 Apr;10(4):556-563. doi: 10.1002/alr.22511. Epub 2019 Dec 20.
Glucocorticoid (GC)-resistant asthma, a complex disease phenotype, has a high morbidity and mortality and takes up a disproportionate share of healthcare costs. The aim of this work was to assess serum 25-hydroxyvitamin D (25(OH)VD) levels in steroid-resistant, steroid-sensitive patients with asthma and in healthy controls, and to investigate the association between the vitamin D receptor gene (VDR) FokI and ApaI polymorphisms and GC resistance in patients with asthma.
This case-control study included 70 patients with severe bronchial asthma and 30 apparently healthy controls. Atopic status was determined by skin-prick test reaction to the most common locally-encountered allergens. A GC reversibility test was performed to differentiate between GC-sensitive and GC-resistant asthma. For all subjects, analysis of the VDR FokI and ApaI polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and measurement of serum 25(OH)VD levels by enzyme-linked immunosorbent assay (ELISA) were performed.
The frequencies of FokI polymorphism genotypes and alleles differed significantly between patients with asthma and controls. The frequencies of the TT genotype and T allele carriers were significantly higher among patients with asthma than among controls, and also among GC-resistant patients with asthma than among GC-sensitive patients with asthma. Additionally, serum 25(OH)VD levels differed significantly among the 3 VDR FokI polymorphic genotypes in GC-resistant patients with asthma; the highest level was detected in the TT genotype. No significant differences in ApaI were found.
We found a possible association between the FokI T allele and GC resistance in patients with asthma. Variations in VDR FokI might also play a role in 25(OH)VD levels.
糖皮质激素（GC）抵抗性哮喘是一种复杂的疾病表型，具有较高的发病率和死亡率，并占用了不成比例的医疗保健费用。本研究旨在评估血清 25-羟维生素 D（25（OH）VD）水平在激素抵抗、激素敏感的哮喘患者和健康对照组中的差异，并探讨维生素 D 受体基因（VDR）FokI 和 ApaI 多态性与哮喘患者 GC 抵抗之间的关系。
这项病例对照研究纳入了 70 名重度支气管哮喘患者和 30 名健康对照者。采用皮肤点刺试验测定特应性状态，检测最常见的局部过敏原。通过 GC 逆转试验区分 GC 敏感和 GC 抵抗性哮喘。对所有受试者进行 VDR FokI 和 ApaI 多态性的聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析，采用酶联免疫吸附试验（ELISA）测定血清 25（OH）VD 水平。
哮喘患者与对照组之间 FokI 多态性基因型和等位基因的频率存在显著差异。哮喘患者 TT 基因型和 T 等位基因携带者的频率显著高于对照组，GC 抵抗性哮喘患者也显著高于 GC 敏感性哮喘患者。此外，GC 抵抗性哮喘患者的 VDR FokI 三种多态性基因型之间的血清 25（OH）VD 水平存在显著差异；TT 基因型的血清 25（OH）VD 水平最高。未发现 ApaI 存在显著差异。
我们发现 FokI T 等位基因与哮喘患者的 GC 抵抗之间可能存在关联。VDR FokI 的变异也可能在 25（OH）VD 水平中起作用。
