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

aspirin-exacerbated 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.