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