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

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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.

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Acknowledgments

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A090548 & 010249), and by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST) (No. 2009-0080157). The DNA samples were generously provided by Soonchunhyang University, Bucheon Hospital Biobank, a member of the National Biobank of Korea, supported by the Ministry of Health, Welfare and Family Affairs, Republic of Korea.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, Republic of Korea

    Byung Lae Park, Joon Seol Bae, Hyun Sub Cheong, Lyoung Hyo Kim & Hyoung Doo Shin

  2. Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul, 121-742, Republic of Korea

    Jeong-Hyun Kim, Charisse Flerida A. Pasaje & Hyoung Doo Shin

  3. Division of Allergy and Respiratory Medicine, Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Bucheon Hospital, 1174, Jung-dong, Wonmi-gu, Bucheon, Gyeonggi-do, 420-020, Republic of Korea

    Tae-Hoon Kim, Jong-Sook Park, SeungWoo Shin & Choon Sik Park

  4. Division of Allergy and Respiratory Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Chungcheongnam-do, Republic of Korea

    Ho Sung Lee

  5. Division of Allergy and Respiratory Medicine, Soonchunhyang University Gumi Hospital, Gumi, Kyungsangbook-do, Republic of Korea

    Myung-Sin Kim

  6. Department of Allergy, Chonnam National University, Gwangju, Republic of Korea

    Inseon S. Choi

  7. Department of Internal Medicine, Chung-Ang University Yongsan Hospital, Seoul, Republic of Korea

    Byoung Whui Choi

  8. Division of Internal Medicine, College of Medicine, Chungbuk National University, 62 Gaesin-dong, Heungduk-gu, Cheongju, Chungcheongbuk-do, 361-711, Republic of Korea

    Mi-Kyeong Kim

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  1. Byung Lae Park
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Correspondence to Hyoung Doo Shin or Choon Sik Park.

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439_2012_1247_MOESM2_ESM.tif

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)

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Park, B.L., Kim, TH., Kim, JH. et al. Genome-wide association study of aspirin-exacerbated respiratory disease in a Korean population. Hum Genet 132, 313–321 (2013). https://doi.org/10.1007/s00439-012-1247-2

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