Influence of vitamin D receptor gene FokI and ApaI polymorphisms on glucocorticoid response in patients with asthma

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.