Kim Seung-Hyun, Cho Bo-Young, Choi Hyunna, Shin Eun-Soon, Ye Young-Min, Lee Jong-Eun, Park Hae-Sim
Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
DNA link, Inc., Seoul, Korea.
PLoS One. 2014 Dec 23;9(12):e111220. doi: 10.1371/journal.pone.0111220. eCollection 2014.
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.
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.
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).
This implies the potential of rs3128965 as a genetic marker for diagnosis and prediction of the AERD phenotype.
乙酰水杨酸（阿司匹林）超敏反应的两种常见临床综合征，即阿司匹林加重性呼吸系统疾病（AERD）和阿司匹林加重性皮肤疾病（AECD），进行了全基因组关联研究，以确定韩国人群中阿司匹林超敏反应的强遗传标记。
对179例AERD患者和1989例健康正常对照者（NC）的Affymetrix全基因组人类SNP芯片上的SNP基因型频率进行比较，发现6号染色体上的SNP与AERD相关，但与AECD无关。为了验证这种关联，我们纳入了第二个队列，包括AERD组（n = 264）、NC组（n = 238）和疾病对照组（阿司匹林耐受哮喘；ATA，n = 387）。
在共显性分析模型中，AERD组中HLA-DPB1区域特定SNP rs3128965的次要基因型频率（AG或AA）高于ATA组或NC组（P = 0.001，P = 0.002）。将rs3128965等位基因与哮喘患者的临床特征进行比较，发现携带A等位基因的患者比不携带A等位基因的患者对吸入阿司匹林和乙酰甲胆碱的支气管高反应性增加，15-HETE水平更高（分别为P = 0.039、0.037和0.004）。
这意味着rs3128965作为AERD表型诊断和预测的遗传标记的潜力。
