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

Background Two common clinical syndromes of acetylsalicylic acid ( aspirin) hypersensitivity, aspirin-exacerbated respiratory disease(AERD) and aspirin-exacerbated cutaneous disease (AECD), were subjected to a genome-wide association study to identify strong genetic markersfor aspirinhypersensitivity in a Korean population. Methods A comparison of SNP genotypefrequencies on an Affymetrix Genome-Wide Human SNP arrayof 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 ( aspirintolerant asthma; ATA, n = 387) groups. Results The minor genotype frequency(AG or AA) of a particular SNP, rs3128965, in the HLA-DPB1region was higher in the AERD group compared to the ATA or NC group (P = 0.001, P = 0.002, in a co- dominant analysismodel, respectively). Comparison of rs3128965 alleles with the clinical features of asthmatics revealed that patients harboring the A allele had increased bronchial hyperresponsivenessto inhaled aspirinand 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 markerfor diagnosis and prediction of the AERD phenotype.