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Letter
Nature Genetics  37, 507 - 513 (2005)
Published online: 17 April 2005; | doi:10.1038/ng1550

A variant in the CD209 promoter is associated with severity of dengue disease

Anavaj Sakuntabhai1, 2, Chairat Turbpaiboon1, 3, Isabelle Casadémont1, Ampaiwan Chuansumrit4, Tassanee Lowhnoo1, 5, 6, Anna Kajaste-Rudnitski7, Sita Mint Kalayanarooj1, 8, Kanchana Tangnararatchakit4, Nattaya Tangthawornchaikul9, Sirijit Vasanawathana10, Wathanee Chaiyaratana6, Pa-thai Yenchitsomanus8, 9, Prapat Suriyaphol8, Panisadee Avirutnan8, Kulkanya Chokephaibulkit11, Fumihiko Matsuda5, Sutee Yoksan12, Yves Jacob13, G Mark Lathrop5, Prida Malasit8, 9, Philippe Desprès7 & Cécile Julier1

1  Génétique des Maladies Infectieuses et Autoimmunes, Institut Pasteur, INSERM E102, 28 rue du docteur Roux, 75724 Paris Cedex 15, France.

2  Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI, Bangkok 10400, Thailand.

3  Department of Biochemistry, Faculty of Science, Ramathibodi Hospital, Mahidol University, Rama VI, Bangkok 10400, Thailand.

4  Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI, Bangkok 10400, Thailand.

5  Centre National de Génotypage, 2 rue Gaston Crémieux, CP 5721, 91057 Evry Cedex, France.

6  Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI, Bangkok 10400, Thailand.

7  Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, 25 rue du docteur Roux, 75724 Paris cedex 15, France.

8  Medical Molecular Biology Unit, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok-noi, Bangkok 10700, Thailand.

9  Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology BIOTEC, National Science and Technology Development Agency NSTDA, Pathumthani 12120, Thailand.

10  Department of Pediatrics, Khon Kaen Hospital, Ministry of Public Health, Khonkaen 40000, Thailand.

11  Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700 Thailand.

12  Center for Vaccine Development, Institute of Science and Technology for Research and Development, Mahidol University, 25/25 Moo 3, Phuttamonthon 4 Road, Salaya, Phuttamonthon District, Nakhon Pathom 73170, Thailand.

13  Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, 25 rue du docteur Roux, 75724 Paris Cedex 15, France.

Correspondence should be addressed to Cécile Julier cjulier@pasteur.fr
Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell−specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells1, 2. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 times 10-7) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 times 10-6). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies.


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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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