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Association of FANCC polymorphisms with FEV1 decline in aspirin exacerbated respiratory disease

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Abstract

Aspirin exacerbated respiratory disease (AERD) is a clinical condition characterized by severe decline in forced expiratory volume in one second (FEV1) following the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. The exacerbated inflammatory response in Fancc-deficient mice has been reported to be associated with hemopoietic responses that are also related to AERD pathogenesis. To investigate associations of FANCC polymorphisms with AERD and related phenotypes, this study genotyped 25 common single nucleotide polymorphisms (SNPs) in a total of 592 Korean asthmatics including 163 AERD and 429 aspirin-tolerant asthma (ATA) subjects. Logistic analysis revealed that genetic polymorphisms of the FANCC gene might not be directly related to AERD development and nasal polyposis (P > 0.05). However, the FEV1 decline by aspirin provocation showed significant associations with FANCC polymorphisms (P = 0.006–0.04) and a haplotype (unique to rs4647416G > A, P = 0.01 under co-dominant, P = 0.006 under recessive model). In silico analysis showed that the “A” allele of rs4647376C > A, which was more prevalent in AERD than in ATA, could act as a potential branch point (BP) site for alternative splicing (BP score = 4.16). Although replications in independent cohorts and further functional evaluations are still needed, our preliminary findings suggest that FANCC polymorphisms might be associated with the obstructive symptoms in allergic diseases.

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Acknowledgments

This work was supported by a grant from the Korea Health 21 R&D Project (A010249) and by grant number M1-0302-00-0073 from the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST) (No. 2009-0080157), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the MEST (No. 2010-0007857).

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Authors and Affiliations

  1. Department of Life Science, Sogang University, Seoul, 121-742, Republic of Korea

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

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

    Byung-Lae Park & Hyoung Doo Shin

  3. Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, 140-743, Republic of Korea

    Jong Sook Park, Sung Woo Park, Soo-Taek Uh & Choon-Sik Park

  4. Division of Allergy and Respiratory Disease, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea

    Jae-Sung Choi & Yong-Hoon Kim

  5. Division of Internal Medicine, Chungbuk National University, Cheongju, Republic of Korea

    Mi-Kyeong Kim

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

    Inseon S. Choi

  7. Department of Internal Medicine and Institute of Allergy and Clinical Immunology, Seoul National University, Seoul, Republic of Korea

    Sang Heon Cho

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

    Byoung Whui Choi

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  1. Jeong-Hyun Kim
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Correspondence to Choon-Sik Park or Hyoung Doo Shin.

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Kim, JH., Park, BL., Pasaje, C.F.A. et al. Association of FANCC polymorphisms with FEV1 decline in aspirin exacerbated respiratory disease. Mol Biol Rep 39, 2385–2394 (2012). https://doi.org/10.1007/s11033-011-0989-6

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  • DOI: https://doi.org/10.1007/s11033-011-0989-6

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