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

Sakuntabhai A, Turbpaiboon C, Casadémont I, Chuansumrit A, Lowhnoo T, Kajaste-Rudnitski A, Kalayanarooj SM, Tangnararatchakit K, Tangthawornchaikul N, Vasanawathana S, Chaiyaratana W, Yenchitsomanus PT, Suriyaphol P, Avirutnan P, Chokephaibulkit K, Matsuda F, Yoksan S, Jacob Y, Lathrop GM, Malasit P, Desprès P, Julier C

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

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 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 x 10(-7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 x 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.

Published 28 April 2005 in Nat Genet, 37(5): 507-13.
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Dengue Fever Books

Dengue and Dengue Hemorrhagic Fever in the Americas: Guidelines for Prevention and Control (Publicaciones Cientificas (Washington, D.C.), No. 548.)

Dengue and Dengue Hemorrhagic Fever in the Americas: Guidelines for Prevention and Control (Publicaciones Cientificas (Washington, D.C.), No. 548.)