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Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness

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Abstract

Airway hyperresponsiveness (AHR) is one of the major clinical symptoms and intermediate phenotypes of asthma. A recent genome-wide search for asthma quantitative trait loci has revealed a significant linkage signal between a p-terminal region of chromosome 2 and AHR. Thus, the gene encoding the potassium voltage-gated channel delayed-rectifier protein S3 (KCNS3) in this region is considered a positional candidate for asthma. We have evaluated a total of 12 single-nucleotide polymorphisms (SNPs) of the KCNS3 gene in a validation panel of 48 lymphoblastoid cell line DNA samples of Chinese origin. Three SNPs were found to be polymorphic and were tested. Two independent sets (an initial screening set and a replication set) of cases and controls from the original linkage study sample were collected. In the initial screening set, two SNPs (rs1031771 and rs1031772) showed suggestive association and were further confirmed by the replication set. In combined single-SNP analysis, the rs1031771 G allele (odds ratio=1.42, P=0.006) and rs1031772 T allele (odds ratio=1.40, P=0.018) were associated with a significantly higher risk of AHR. Haplotype analysis also detected significant association (P=0.006). Our findings suggest that SNPs located at the 3′ downstream region of KCNS3 have a significant role in the etiology of AHR.

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Acknowledgements

This study was supported by the National Institutes of Health grant HL066385. We are grateful for the assistance and cooperation of the faculty and staff of the Anhui Medical University Biomedical Institute, and we thank all study participants for their support.

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Authors and Affiliations

  1. Program for Population Genetics, Harvard School of Public Health, 665 Huntington Avenue FXB-101, Boston, MA 02115, USA

    Ke Hao, Tianhua Niu, Xin Xu & Xiping Xu

  2. Department of Biostatistics, Harvard School of Public Health, Boston, Mass., USA

    Ke Hao

  3. Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass., USA

    Tianhua Niu

  4. Anqing Biomedical Institute, Anhui Medical University, Anhui, China

    Zhian Fang, Xiping Xu & Xiping Xu

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  1. Ke Hao
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  2. Tianhua Niu
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  5. Xiping Xu
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Correspondence to Xiping Xu.

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Hao, K., Niu, T., Xu, X. et al. Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness. Hum Genet 116, 378–383 (2005). https://doi.org/10.1007/s00439-005-1256-5

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  • DOI: https://doi.org/10.1007/s00439-005-1256-5

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