The Association of a Single-Nucleotide Polymorphism of the IL-2 Inducible T-cell Kinase Gene with Asthma

Authors

  • Shin-Hwa Lee,

    1. Asthma Genome Research Group, Soonchunhyang University Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do 420–020, Korea
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  • Hun Soo Chang,

    1. Asthma Genome Research Group, Soonchunhyang University Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do 420–020, Korea
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  • An-Soo Jang,

    1. Asthma Genome Research Group, Soonchunhyang University Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do 420–020, Korea
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  • Sung-Woo Park,

    1. Asthma Genome Research Group, Soonchunhyang University Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do 420–020, Korea
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  • Jong Sook Park,

    1. Asthma Genome Research Group, Soonchunhyang University Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do 420–020, Korea
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  • Soo-Taek Uh,

    1. Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, 657, Hannam-Dong, Yongsan-Gu, Seoul 140–743, Korea
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  • Yong Hoon Kim,

    1. Division of Allergy and Respiratory Medicine, Soonchunhyang University Cheonan Hospital, 23–20, Bongmyeong-dong, Cheonan, Chungcheongnam-do 330–721, Korea
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  • Bermseok Oh,

    1. Department of Biomedical Engineering, School of Medicine, Kyunghee University, Hoegi-Dong Dongdaemun-Gu, Seoul 130–701, Korea
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  • Jong-Keuk Lee,

    1. Asan Institute for Life Sciences, University of Ulsan College of Medicine, Pungnap-dong, Songpa-ku, Seoul 138–736, Korea
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  • Byung-Lae Park,

    1. Department of Genetic Epidemiology, SNP-Genetics Inc., B-1407, WooLim Lion's Valley, 371–28 Gasan-Dong, Geumcheon-Ku, Seoul 153–803, Korea
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  • Hyung Doo Shin,

    1. Department of Genetic Epidemiology, SNP-Genetics Inc., B-1407, WooLim Lion's Valley, 371–28 Gasan-Dong, Geumcheon-Ku, Seoul 153–803, Korea
    2. Department of Life Science, Sogang University, Sinsu-dong, Mapo-gu, Seoul 121–742, Korea
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  • Choon-Sik Park,

    Corresponding author
    1. Asthma Genome Research Group, Soonchunhyang University Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do 420–020, Korea
      Corresponding author: Choon-Sik Park, Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-Dong, Wonmi-Ku, Bucheon, Kyeonggi-Do 420–767, Korea. Tel.: +82326215105;
      Fax: +82326215023; E-mail: mdcspark@unitel.co.kr
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  • Kuchan Kimm

    1. National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, Seoul 122–701, Korea
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Corresponding author: Choon-Sik Park, Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-Dong, Wonmi-Ku, Bucheon, Kyeonggi-Do 420–767, Korea. Tel.: +82326215105;
Fax: +82326215023; E-mail: mdcspark@unitel.co.kr

Summary

Asthma manifests as TH2-dominant airway inflammation regulated by inducible T-cell kinase (ITK). To investigate associations between genetic variants of the ITK gene and asthma, 31 single-nucleotide polymorphisms (SNPs) were genotyped in 303 normal controls and 498 asthmatics and the two groups were compared using logistic regression models. The functional effects of the ITK promoter SNP were assessed using pGL3 luciferase reporter systems and gel-shift assays. The minor allele−196C>T in the promoter region of the ITK gene was significantly more frequent in asthmatics than in controls. The luciferase activity of the PGL3-ITK-196T allele construct was higher than that of the −196C allele. In the gel-shift assay, −196T double-stranded oligonucleotides bound more strongly to Jurkat cell nuclear protein compared to the −196C double-stranded oligonucleotides. People with the −rare allele 196C>T may be more susceptible to asthma via transcriptional regulation of the ITK gene.

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