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Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis

Genes & Immunity volume 11, pages 416–422 (2010)Cite this article

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Abstract

Chromosome 5q31 spans the T helper (Th) 2-related cytokine gene cluster, which is potentially important in Th1/Th2 immune responses. The chromosome 5q23.2–31.3 has been recently identified as a region with suggestive evidence of linkage to tuberculosis in the Asian population. With the aim of fine-mapping a putative tuberculosis susceptibility locus, we investigated a family-based association test between the dense single nucleotide polymorphism (SNP) markers within chromosome 5q31 and tuberculosis in 205 Thai trio families. Of these, 75 SNPs located within candidate genes covering SLC22A4, SLC22A5, IRF1, IL5, RAD50, IL13, IL4, KIF3A and SEPT8 were genotyped using the DigiTag2 assay. Association analysis revealed the most significant association with tuberculosis in haplotypes comprising SNPs rs274559, rs274554 and rs274553 of SLC22A5 gene (PGlobal=2.02 × 10−6), which remained significant after multiple testing correction. In addition, two haplotypes within the SLC22A4 and KIF3A region were associated with tuberculosis. Haplotypes of SLC22A5 were significantly associated with the expression levels of RAD50 and IL13. The results show that the variants carried by the haplotypes of SLC22A4, SLC22A5 and KIF3A region potentially contribute to tuberculosis susceptibility among the Thai population.

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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 and intramural grant from Department of Medical Sciences, Ministry of Public Health, Thailand. We thank all staffs and collaborators of the TB/HIV research project, Thailand, a collaborative research project between the Research Institute of Tuberculosis (RIT) and the Japan Anti-tuberculosis Association, and the Department of Medical Sciences, Ministry of Public Health for collecting the clinical information and samples.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Mahidol University, Bangkok, Thailand

    C Ridruechai & S Khusmith

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

    S Mahasirimongkol, J Phromjai, H Yanai, N Yamada & S Moolphate

  3. Department of Medical Sciences, National Institute of Health, Ministry of Public Health, Nonthaburi, Thailand

    S Mahasirimongkol & P Sawanpanyalert

  4. Department of Clinical Laboratory, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan

    H Yanai

  5. Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    N Nishida & K Tokunaga

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

    I Matsushita & N Keicho

  7. Doctoral Programme in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

    J Ohashi

  8. Chiang Rai Provincial Health Office, Office of the Permanent Secretary, Ministry of Public Health, Chiang Rai, Thailand

    S Summanapan

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

    C Chuchottaworn

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

    W Manosuthi

  11. Department of Medicine, 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 Kanitvittaya

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  1. C Ridruechai
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Correspondence to K Tokunaga.

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Ridruechai, C., Mahasirimongkol, S., Phromjai, J. et al. Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis. Genes Immun 11, 416–422 (2010). https://doi.org/10.1038/gene.2010.26

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  • DOI: https://doi.org/10.1038/gene.2010.26

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