ABCC4 gene Polymorphism Is Associated with High Periostin Levels in Asthmatic Patients

Background: ABCC4 (ATP-binding cassette, sub-family C, member 4) is a protein-coding gene which codes for transmembrane protein. ABCC4 protein transports various molecules across extra- and intra-cellullar membranes, including PGE₂ and cAMP. Studies have reported that PGE₂ and cAMP play an important role in the regulation of immune responses and airway inflammation. In this study, we investigated the associations of ABCC4 gene polymorphisms and clinical characteristics of asthmatic patients to understand the role of ABCC4gene in asthma pathogenesis.

Methods: 269 asthma patients and 118 normal healthy controls were enrolled in the study. Two single nucleotide polymorphisms (SNP) (-642G>C and -1508A>G) in the ABCC4promoter region were genotyped by TaqMan allelic discrimination assay. Functional variabilities in the promoter polymorphisms were analyzed by gene reporter assay. Inflammatory cytokine levels in serum were measured by ELISA.

Results: There were no significant differences in genotype frequencies between two study groups. Asthmatic patients carrying G allele at -1508A>G had significantly higher periostin levels in sera (P=0.018) and lower PC₂₀ methacholine levels (P=0.008) compared to non-carriers. No significant difference was noted in sputum eosinophil count according to each genotype. Gene reporter assay showed that the promoter SNP tagged by G-1508 allele conferred significantly higher promoter activity (P<0.01) compared with A-1508 allele in A549 cell line.

Conclusion: These findings suggest that ABCC4 gene polymorphism at -1508A>G may enhance periostin production and could involve in eosinophilic asthma.