title: A variant in the CD209 promoter is associated with severity of dengue disease.
abstract: 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.
authors.affiliation: Génétique des Maladies Infectieuses et Autoimmunes, Institut Pasteur, INSERM E102, 28 rue du docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Anavaj
authors.initials: A
authors.lastname: Sakuntabhai
authors.forename: Chairat
authors.initials: C
authors.lastname: Turbpaiboon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Casadémont
authors.forename: Ampaiwan
authors.initials: A
authors.lastname: Chuansumrit
authors.forename: Tassanee
authors.initials: T
authors.lastname: Lowhnoo
authors.forename: Anna
authors.initials: A
authors.lastname: Kajaste-Rudnitski
authors.forename: Sita Mint
authors.initials: SM
authors.lastname: Kalayanarooj
authors.forename: Kanchana
authors.initials: K
authors.lastname: Tangnararatchakit
authors.forename: Nattaya
authors.initials: N
authors.lastname: Tangthawornchaikul
authors.forename: Sirijit
authors.initials: S
authors.lastname: Vasanawathana
authors.forename: Wathanee
authors.initials: W
authors.lastname: Chaiyaratana
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.forename: Prapat
authors.initials: P
authors.lastname: Suriyaphol
authors.forename: Panisadee
authors.initials: P
authors.lastname: Avirutnan
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Sutee
authors.initials: S
authors.lastname: Yoksan
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacob
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.forename: Cécile
authors.initials: C
authors.lastname: Julier
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics*; D003715:Dengue / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012720:Severity of Illness Index; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin