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

Abstract

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.