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TitleThe rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma
Author(s)Carvalho, Agostinho
Cunha, Cristina
Almeida, A. J.
Osório, Nuno S.
Saraiva, Margarida
Coelho, Maria Teixeira
Pedreiro, Susana
Torrado, Egídio
Domingues, Nelson
Marques, António
Lacerda, João F.
Silva, Maria Gomes da
Gomes, Marília
Pinto, Ana C.
Torres, Fátima
Rendeiro, Paula
Tavares, Purificação
Ianni, Mauro de
Medeiros, Rui
Heutink, Peter
Bracci, Paige M.
Conde, Lucia
Ludovico, Paula
Pedrosa, Jorge
Maciel, P.
Pitzurra, Lucia
Aversa, Franco
Marques, Herlander
Paiva, Artur
Skibola, Christine F.
Romani, Luigina
Castro, António G.
Rodrigues, Fernando José dos Santos
Keywordstoll-like receptors
non-Hodgkin lymphoma
single nucleotide polymorphism
Issue dateFeb-2012
PublisherNature Publishing Group
JournalGenes and Immunity
Abstract(s)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.
DescriptionWe 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
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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