Toll-Like Receptor 4 Polymorphisms in Dengue Virus–Infected Children

Kis Djamiatun Department of Parasitology, and Division of Human Genetics, Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia; Department of Internal Medicine, and Nijmegen Center for Infection, Inflammation and Immunity, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands

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Bart Ferwerda Department of Parasitology, and Division of Human Genetics, Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia; Department of Internal Medicine, and Nijmegen Center for Infection, Inflammation and Immunity, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands

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Mihai G. Netea Department of Parasitology, and Division of Human Genetics, Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia; Department of Internal Medicine, and Nijmegen Center for Infection, Inflammation and Immunity, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands

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André J. A. M. van der Ven Department of Parasitology, and Division of Human Genetics, Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia; Department of Internal Medicine, and Nijmegen Center for Infection, Inflammation and Immunity, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands

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Wil M. V. Dolmans Department of Parasitology, and Division of Human Genetics, Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia; Department of Internal Medicine, and Nijmegen Center for Infection, Inflammation and Immunity, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands

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Sultana M. H. Faradz Department of Parasitology, and Division of Human Genetics, Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia; Department of Internal Medicine, and Nijmegen Center for Infection, Inflammation and Immunity, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands

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Differential viral recognition by cells bearing Toll-like receptor 4 (TLR4) polymorphisms Asp299Gly and Thr399Ile may influence susceptibility and severity of dengue virus infection. In central Java, Indonesia, we investigated 201 children with dengue hemorrhagic fever (DHF) and 179 healthy controls. Patients and controls were mostly ethnic Javanese. A nearly complete cosegregation of the two mutations was observed. The TLR4 299/399 genotype was found in five patients and four controls. Prevalence of the TLR4 299/399 genotype did not differ significantly between controls and DHF patients or between patients with different severities of DHF. Also, vascular leakage in patients with different TLR4 genotypes did not differ. Thus, the 299/399 TLR4 haplotype has only minor influence on susceptibility and severity of complicated dengue virus infection.

Author Notes

*Address correspondence to Kis Djamiatun, Parasitology Department, Faculty of Medicine, Diponegoro University, Jl. Sriwijaya 34, Post code 50242, Semarang, Indonesia. E-mail: ramus64@yahoo.com

Financial support: Mihai G. Netea was supported by a Vici Grant from the Netherlands Organization for Scientific Research. Kis Djamiatun was recipient by a PhD Fellowship from Ministry of National Education, Republic of Indonesia.

Authors' addresses: Kis Djamiatun, Parasitology Department, Faculty of Medicine, Diponegoro University, Jl. Sriwijaya 34, Semarang, Indonesia, E-mail: ramus64@yahoo.com. Bart Ferwerda, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, E-mail: ferwerda@mail.med.upenn.edu. Mihai G. Netea, André J. A. M. van der Ven, and Will M. V. Dolmans, Department of General Internal Medicine, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands, E-mails: m.netea@aig.umcn.nl, a.vanderven@aig.umcn.nl, and dolmansw@xs4all.nl. Sultana M. H. Faradz, Division of Human Genetics, Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia, E-mail: sultana@indosat.net.id.

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