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

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; Malasit, Prida; Desprès, Philippe; Julier, Cécile

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(1,2). 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ng1550) contains supplementary material, which is available to authorized users.