1. A variant in the CD209 promoter is associated with severity of dengue disease.
- Author
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Sakuntabhai, Anavaj, Turbpaiboon, Chairat, Casadémont, Isabelle, Chuansumrit, Ampaiwan, Lowhnoo, Tassanee, Kajaste-Rudnitski, Anna, Kalayanarooj, Sita Mint, Tangnararatchakit, Kanchana, Tangthawornchaikul, Nattaya, Vasanawathana, Sirijit, Chaiyaratana, Wathanee, Yenchitsomanus, Pa-thai, Suriyaphol, Prapat, Avirutnan, Panisadee, Chokephaibulkit, Kulkanya, Matsuda, Fumihiko, Yoksan, Sutee, Jacob, Yves, Lathrop, G Mark, and Malasit, Prida
- Subjects
DENGUE ,MOSQUITOES ,DENDRITIC cells ,HEMORRHAGIC fever ,COHORT analysis - 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 = 1.4×10
-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. [ABSTRACT FROM AUTHOR]- Published
- 2005
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