Polymorphisms of the vitamin D-binding protein (DBP) gene in Japanese patients with aspirin-exacerbated respiratory disease (AERD)

AERD is known to represent acute asthmatic attacks by means of ingestion of aspirin and other non-steroidal anti-inflammatory drug(NSAID).Individuals with AERD are more commonly found in middle-aged female, and their asthmatic symptoms tend to be chronic, perennial and severe. However, the pathophysiologic mechanisms underlying the development of this specific asthma phenotype have not yet been fully understood. Recent studies have reported that levels of DBP in the airway are elevated in children with severe asthma. In this study, we examined the DBP gene polymorphisms in a Japanese adult population. Methods: DNA specimens were obtained from the following three groups:100 patients with AERD, 100 patients with aspirin-tolerant asthma(ATA), and 50 normal controls. Allelic discrimination assay for single nucleotide polymorphisms(SNPs) relating to the DBP gene expression was carried out by using previously described SNPs detective system, sequence-specific thermal-elution chromatography. Results: The frequencies of the CT/TT genotype of DBP(rs4588) were higher than those of the CC genotype in AERD patients compared to ATA patients(P=0.002). In female AERD patients, but not in males, frequencies of the CT/TT genotype were higher than those of the CC genotype of DBP compared to female ATA patients(P=0.004). Furthermore, in AERD patients, the eosinophil counts of the CT/TT genotype of DBP were higher than those of the CC genotype(P=0.046). Conclusions: We were the first to analyze DBP gene polymorphism in Japanese patients with AERD, and showed that DBP gene polymorphism in Japanese patients with AERD is different from that in the patients with ATA.