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The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma

Genes & Immunity volume 13, pages 197–201 (2012)Cite this article

Abstract

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case–control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E−9) and Italian (OR, 1.84; P=6.0E−5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.

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Acknowledgements

AC, NSO, MTC and AJA were financially supported by a fellowship from Fundação para a Ciência e Tecnologia, Portugal. MS is a Ciência 2007 fellow. This study was supported by Fundação para a Ciência e Tecnologia, Portugal (PIC/IC/83313/2007) and by Fundação Calouste Gulbenkian, Serviço de Saúde e Desenvolvimento Humano, Portugal (Grant Number:Proc/60666-MM/734). CFS, PB and LC were supported by National Institutes of Health (NIH) grants CA122663 and CA104682, and PB also by NIH grants CA45614 and CA89745. We are grateful to Paulo Vieira, Cecília Leão, Manuel T Silva, Nuno Sousa, Jorge Correia-Pinto, Joana Palha, Margarida Correia-Neves, Margarida Lima and Matthew Berry for all their input throughout these studies and critical reading of the manuscript. We are grateful to the patients who joint this study, as well as to all members of the Life and Health Sciences Research Institute and School of Health Sciences, University of Minho, who contributed in any way to the development of this work.

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  1. A G Castro and F Rodrigues: These authors share author leadership.

Authors and Affiliations

  1. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

    A Carvalho, C Cunha, A J Almeida, N S Osório, M Saraiva, M Teixeira-Coelho, E Torrado, A G Gomes-Alves, P Ludovico, J Pedrosa, P Maciel, A G Castro & F Rodrigues

  2. ICVS/3B's—PT Government Associate Laboratory, Braga/Guimarães, Portugal

    A Carvalho, C Cunha, A J Almeida, N S Osório, M Saraiva, M Teixeira-Coelho, E Torrado, A G Gomes-Alves, P Ludovico, J Pedrosa, P Maciel, A G Castro & F Rodrigues

  3. Department of Experimental Medicine and Biochemical Sciences, Microbiology Section, University of Perugia, Perugia, Italy

    A Carvalho, C Cunha, L Pitzurra & L Romani

  4. Centro de Histocompatibilidade do Centro, Coimbra, Portugal

    S Pedreiro & A Paiva

  5. Portuguese Institute of Oncology, Porto, Portugal

    N Domingues & R Medeiros

  6. Hospital de São Marcos, Braga, Portugal

    A Marques & H Marques

  7. Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal

    J F Lacerda

  8. Department of Haematology, Portuguese Institute of Oncology, Lisbon, Portugal

    M G da Silva

  9. Portuguese Institute of Oncology, Coimbra, Portugal

    M Gomes & A C Pinto

  10. CGC—Centro de Genética Clínica, Porto, Portugal

    F Torres, P Rendeiro & P Tavares

  11. Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy

    M Di Ianni & F Aversa

  12. Department of Clinical Genetics, Section Medical Genomics, VU University Medical Center, Amsterdam, The Netherlands

    P Heutink

  13. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

    P M Bracci

  14. Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA

    L Conde & C F Skibola

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Correspondence to F Rodrigues.

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Carvalho, A., Cunha, C., Almeida, A. et al. The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma. Genes Immun 13, 197–201 (2012). https://doi.org/10.1038/gene.2011.59

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