Human Genetics

, Volume 132, Issue 3, pp 313–321

Genome-wide association study of aspirin-exacerbated respiratory disease in a Korean population

  • Byung Lae Park
  • Tae-Hoon Kim
  • Jeong-Hyun Kim
  • Joon Seol Bae
  • Charisse Flerida A. Pasaje
  • Hyun Sub Cheong
  • Lyoung Hyo Kim
  • Jong-Sook Park
  • Ho Sung Lee
  • Myung-Sin Kim
  • Inseon S. Choi
  • Byoung Whui Choi
  • Mi-Kyeong Kim
  • SeungWoo Shin
  • Hyoung Doo Shin
  • Choon Sik Park
Original Investigation

DOI: 10.1007/s00439-012-1247-2

Cite this article as:
Park, B.L., Kim, TH., Kim, JH. et al. Hum Genet (2013) 132: 313. doi:10.1007/s00439-012-1247-2

Abstract

Aspirin-exacerbated respiratory disease (AERD) is a nonallergic clinical syndrome characterized by a severe decline in forced expiratory volume in one second (FEV1) following the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin. The effects of genetic variants have not fully explained all of the observed individual differences to an aspirin challenge despite previous attempts to identify AERD-related genes. In the present study, we performed genome-wide association study (GWAS) and targeted association study in Korean asthmatics to identify new genetic factors associated with AERD. A total of 685 asthmatic patients without AERD and 117 subjects with AERD were used for the GWAS of the first stage, and 996 asthmatics without AERD and 142 subjects with AERD were used for a follow-up study. A total of 702 SNPs were genotyped using the GoldenGate assay with the VeraCode microbead. GWAS revealed the top-ranked variants in 3′ regions of the HLA-DPB1 gene. To investigate the detailed genetic effects of an associated region with the risk of AERD, a follow-up targeted association study with the 702 single nucleotide polymorphisms (SNPs) of 14 genes was performed on 802 Korean subjects. In a case–control analysis, HLA-DPB1 rs1042151 (Met105Val) shows the most significant association with the susceptibility of AERD (p = 5.11 × 10−7; OR = 2.40). Moreover, rs1042151 also shows a gene dose for the percent decline of FEV1 after an aspirin challenge (p = 2.82 × 10−7). Our findings show that the HLA-DPB1 gene polymorphism may be the most susceptible genetic factor for the risk of AERD in Korean asthmatics and confirm the importance of HLA-DPB1 in the genetic etiology of AERD.

Supplementary material

439_2012_1247_MOESM1_ESM.xls (465 kb)
Supplementary Tables (XLS 465 kb)
439_2012_1247_MOESM2_ESM.tif (2.7 mb)
Supplementary Figure 1 Supplementary Figure 1. The eQTL result of rs1042151 of HLA-DPB1. Red box indicates eQTL rs1042151 of HLA-DPB1 derived from the eQTL browser (http://eqtl.uchicago.edu/cgi-bin/gbrowse/eqtl/) (TIFF 2722 kb)
439_2012_1247_MOESM3_ESM.doc (22 kb)
Supplementary material 3 (DOC 22 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Byung Lae Park
    • 1
  • Tae-Hoon Kim
    • 3
  • Jeong-Hyun Kim
    • 2
  • Joon Seol Bae
    • 1
  • Charisse Flerida A. Pasaje
    • 2
  • Hyun Sub Cheong
    • 1
  • Lyoung Hyo Kim
    • 1
  • Jong-Sook Park
    • 3
  • Ho Sung Lee
    • 4
  • Myung-Sin Kim
    • 5
  • Inseon S. Choi
    • 6
  • Byoung Whui Choi
    • 7
  • Mi-Kyeong Kim
    • 8
  • SeungWoo Shin
    • 3
  • Hyoung Doo Shin
    • 1
    • 2
  • Choon Sik Park
    • 3
  1. 1.Department of Genetic EpidemiologySNP Genetics, IncSeoulRepublic of Korea
  2. 2.Department of Life ScienceSogang UniversitySeoulRepublic of Korea
  3. 3.Division of Allergy and Respiratory Medicine, Genome Research Center for Allergy and Respiratory DiseasesSoonchunhyang University Bucheon HospitalBucheonRepublic of Korea
  4. 4.Division of Allergy and Respiratory MedicineSoonchunhyang University Cheonan HospitalCheonanRepublic of Korea
  5. 5.Division of Allergy and Respiratory MedicineSoonchunhyang University Gumi HospitalGumiRepublic of Korea
  6. 6.Department of AllergyChonnam National UniversityGwangjuRepublic of Korea
  7. 7.Department of Internal MedicineChung-Ang University Yongsan HospitalSeoulRepublic of Korea
  8. 8.Division of Internal MedicineCollege of Medicine, Chungbuk National UniversityCheongjuRepublic of Korea