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Genome-wide SNP-based linkage analysis of tuberculosis in Thais

Genes & Immunity volume 10, pages 77–83 (2009)Cite this article

Abstract

Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide. Human protective immunity that contains tuberculosis after infection has not been clearly defined. To gain insight into host genetic factors, nonparametric linkage analysis was performed using high-throughput microarray-based single nucleotide polymorphism (SNP) genotyping platform, a GeneChip array comprised 59 860 bi-allelic markers, in 93 Thai families with multiple siblings, 195 individuals affected with tuberculosis. Genotyping revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis (Z(lr) statistics=3.01, logarithm of odds (LOD) score=2.29, empirical P-value=0.0005), and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate (maximum LOD score=2.57 and 3.33, permutation P-value=0.0187 and 0.0183, respectively). These results imply a new evidence of genetic risk factors for tuberculosis in the Asian population. The significance of these ordered subset results supports a clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients. The linkage information from a specific ethnicity may provide unique candidate regions for the identification of the susceptibility genes and further help elucidate the immunopathogenesis of tuberculosis.

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Acknowledgements

This study was partly supported by International Cooperation Research Grant, the Ministry of Health, Labor and Welfare from 2002 to 2004 and by a Grant-in-Aid for Scientific Research on Priority Areas ‘Comprehensive Genomics’ from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Ms Masako Okochi (International Medical Center of Japan) for technical support. We extend their appreciation to all of the staff and collaborators of the TB/HIV Research Project, Thailand, a collaborative research project between the Research Institute of Tuberculosis (RIT), the Japan Anti-tuberculosis Association and the Thai Ministry of Public Health for collecting the clinical information and samples.

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Authors and Affiliations

  1. Department of Medical Sciences, Medical Genetic Section, National Institute of Health, Ministry of Public Health, Nonthaburi, Thailand

    S Mahasirimongkol & P Sawanpanyalert

  2. TB/HIV Research Project, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Chiang Rai, Thailand

    S Mahasirimongkol, H Yanai, N Yamada & S Moolphate

  3. Center for Collaborative Research and Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

    H Yanai

  4. Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan

    N Nishida, J Ohashi & K Tokunaga

  5. Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    C Ridruechai & S Khusmith

  6. Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Shinjuku-ku, Tokyo, Japan

    I Matsushita & N Keicho

  7. Chiang Rai Provincial Health Office, Ministry of Public Health, Chiang Rai, Thailand

    S Summanapan

  8. Department of Medical Services, Chest Disease Institute, Ministry of Public Health, Nonthaburi, Thailand

    C Chuchotaworn

  9. Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    A Chaiprasert

  10. Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand

    W Manosuthi

  11. Chiang Rai Regional Hospital, Ministry of Public Health, Chiang Rai, Thailand

    P Kantipong

  12. Department of Medical Sciences, Chiang Rai Regional Medical Sciences Center, Ministry of Public Health, Chiang Rai, Thailand

    S Kanitwittaya

  13. Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    T Sura

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  1. S Mahasirimongkol
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Correspondence to N Keicho.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Mahasirimongkol, S., Yanai, H., Nishida, N. et al. Genome-wide SNP-based linkage analysis of tuberculosis in Thais. Genes Immun 10, 77–83 (2009). https://doi.org/10.1038/gene.2008.81

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