Nature genetics · 2005
A variant in the CD209 promoter is associated with severity of dengue disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, Malasit Prida, Desprès Philippe, Julier Cécile
Аннотация
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.