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Title: A variant in the CD209 promoter is associated with severity of dengue disease
Authors: Anavaj Sakuntabhai
Chairat Turbpaiboon
Isabelle Casadémont
Ampaiwan Chuansumrit
Tassanee Lowhnoo
Anna Kajaste-Rudnitski
Sita Mint Kalayanarooj
Kanchana Tangnararatchakit
Nattaya Tangthawornchaikul
Sirijit Vasanawathana
Wathanee Chaiyaratana
Pa Thai Yenchitsomanus
Prapat Suriyaphol
Panisadee Avirutnan
Kulkanya Chokephaibulkit
Fumihiko Matsuda
Sutee Yoksan
Yves Jacob
G. Mark Lathrop
Prida Malasit
Philippe Desprès
Cécile Julier
Institut Pasteur, Paris
Mahidol University
Centre National de Genotypage
Thailand National Center for Genetic Engineering and Biotechnology
Khon Kaen Regional Hospital
The Institute of Science and Technology for Research and Development, Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-May-2005
Citation: Nature Genetics. Vol.37, No.5 (2005), 507-513
Abstract: Dengue fever and dengue hemorrhagic fever are mosquitoborne 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 cells. 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 × 10-7) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 × 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.
ISSN: 10614036
Appears in Collections:Scopus 2001-2005

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