The SNP rs3128965 of HLA-DPB1 as a genetic marker of the AERD phenotype

Abstract

Background: Two common clinical syndromes of acetylsalicylic acid (aspirin) hypersensitivity, aspirin-exacerbated respiratory disease (AERD) and aspirinexacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markers for aspirin hypersensitivity in a Korean population. Methods: A comparison of SNP genotype frequencies on an Affymetrix Genome-Wide Human SNP array of 179 AERD patients and 1989 healthy normal control subjects (NC) revealed SNPs on chromosome 6 that were associated with AERD, but not AECD. To validate the association, we enrolled a second cohort comprising AERD (n=264), NC (n=238) and disease-control (aspirin tolerant asthma; ATA, n=387) groups. Results: The minor genotype frequency (AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1 region was higher in the AERD group compared to the ATA or NC group (P =0.001, P= 0.002, in a co-dominant analysis model, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsiveness to inhaled aspirin and methacholine, and higher 15-HETE levels, than those without the A allele (P=0.039, 0.037, and 0.004, respectively). Conclusions: This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype.