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

Anavaj Sakuntabhai, Chairat Turbpaiboon, Isabelle Casadémont, Ampaiwan Chuansumrit, Tassanee Lowhnoo, Anna Kajaste-Rudnitski, Sita Mint Kalayanarooj, Kanchana Tangnararatchakit, Nattaya Tangthawornchaikul, Sirijit Vasanawathana, Wathanee Chaiyaratana, Pa Thai Yenchitsomanus, Prapat Suriyaphol, Panisadee Avirutnan, Kulkanya Chokephaibulkit, Fumihiko Matsuda, Sutee Yoksan, Yves Jacob, G. Mark Lathrop, Prida MalasitPhilippe Desprès, Cécile Julier

Research output: Contribution to journalArticle

Abstract

Dengue fever and dengue hemorrhagic fever are mosquitoborne 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.

Original languageEnglish
Pages (from-to)507-513
Number of pages7
JournalNature Genetics
Volume37
Issue number5
DOIs
Publication statusPublished - May 2005

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ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Sakuntabhai, A., Turbpaiboon, C., Casadémont, I., Chuansumrit, A., Lowhnoo, T., Kajaste-Rudnitski, A., Kalayanarooj, S. M., Tangnararatchakit, K., Tangthawornchaikul, N., Vasanawathana, S., Chaiyaratana, W., Yenchitsomanus, P. T., Suriyaphol, P., Avirutnan, P., Chokephaibulkit, K., Matsuda, F., Yoksan, S., Jacob, Y., Lathrop, G. M., ... Julier, C. (2005). A variant in the CD209 promoter is associated with severity of dengue disease. Nature Genetics, 37(5), 507-513. https://doi.org/10.1038/ng1550