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Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations

Nature Genetics volume 40, pages 261–262 (2008)Cite this article

To the Editor:

Khor et al.1 have recently reported an association of four different infectious diseases, including tuberculosis, with the amino acid–changing polymorphism rs8177374 (C→T, S180L) in the toll-interleukin-1 receptor domain–containing adaptor protein (TIRAP, also known as MyD88 adaptor-like, or MAL). This association was observed across a wide range of populations, and its estimated effect in tuberculosis (odds ratio (OR) = 0.23) was considerably larger than the confirmed effects of the causal polymorphisms in other complex diseases (0.5 < OR < 2)2,3,4,5. The tuberculosis associations in Khor et al. were observed in 675 patients and 605 controls from West Africa (a combined sample of individuals from Gambia, Guinea-Bissau and the Republic of Guinea; P = 0.013), and in families from West Africa and Algeria (Pone-tailed = 0.075 and 0.02, respectively).

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Acknowledgements

We are grateful to all study participants. We thank L. Stcheglova and Y. Korneev, I. Fedorin, N. Lebedeva and S. Zakharova for their help in recruiting study participants and collecting blood samples in Russia, as well as E. Browne, T. Enimil, J. Gyapong, I. Osei and E. Owusu-Dabo for their contributions to the study in Ghana. We thank M. Netea and A. Thalamuthu for helpful suggestions and discussions. S.N. is a Diabetes Research and Wellness Foundation Non-Clinical Fellow. The Diabetes and Inflammation Laboratory is funded by the Juvenile Diabetes Research Foundation and the Wellcome Trust. Recruitment and analysis of the Ghanaian study group were supported by the German Ministry for Education and Research through the National Genome Research Network. The Indonesian study was supported by the Royal Academy of Arts and Sciences (KNAW), the Netherlands, the research network PRIOR (Poverty Related Infection Oriented Research), The Netherlands Foundation for Advancement of Tropical Research (NWO-WOTRO), the Eijkman Institute of Molecular Biology, Jakarta, and the Genome Institute of Singapore. The funders had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or the preparation, review and approval of the manuscript.

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Authors and Affiliations

  1. Department of Medical Genetics, Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK

    Sergey Nejentsev, Jeffrey S Szeszko, Helen Stevens & John A Todd

  2. Department of Molecular Medicine, Bernhard Nocht Institute for Topical Medicine, Hamburg, 20359, Germany

    Thorsten Thye & Rolf D Horstmann

  3. University Hospital Schleswig-Holstein, Campus Lübeck, Institute of Medical Biometry and Statistics, Lübeck, 23538, Germany

    Thorsten Thye

  4. Health Protection Agency Mycobacterium Reference Unit and Clinical TB and HIV Group, Center for Infectious Diseases, Institute for Cell and Molecular Sciences, Barts and the London Medical School, London, E1 2AT, UK

    Yanina Balabanova & Francis Drobniewski

  5. Samara Region Tuberculosis Service, Samara, Russian Federation

    Yanina Balabanova

  6. Health Research Unit, Ghana Health Service, GP-184, Accra, Ghana

    Amanua M Chinbuah

  7. Population Genetics and Genetic Epidemiology, Genome Institute of Singapore, 138672, Singapore

    Martin Hibberd, Eileen Png & Mark Seielstad

  8. Department of Immunohematology and Blood Transfusion and Department of Infectious Diseases, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands

    Esther van de Vosse & Tom H M Ottenhoff

  9. Division of Tropical and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia

    Bachti Alisjahbana

  10. Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, 6500 HB, The Netherlands

    Reinout van Crevel

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Correspondence to Sergey Nejentsev.

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Supplementary Note, Supplementary Table 1 and Supplementary Methods (PDF 180 kb)

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Nejentsev, S., Thye, T., Szeszko, J. et al. Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations. Nat Genet 40, 261–262 (2008). https://doi.org/10.1038/ng0308-261

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