Dengue hemorrhagic fever is associated with polymorphisms in JAK1

Abstract

To identify genes associated with the clinical presentation of dengue, 50 cases of probable or possible dengue hemorrhagic fever, 236 dengue fever and 236 asymptomatic infections were genotyped for 593 single nucleotide polymorphisms in 56 genes across the type 1 interferon response pathway as well as other important candidate genes. By single locus analysis comparing dengue hemorrhagic fever with dengue fever, 11 of the 51 markers with p<0.05 were in the JAK1 gene. Five markers were significantly associated by false discovery rate criteria (q<0.20 when p<6 × 10−4). The JAK1 single nucleotide polymorphisms showed differential distribution by ethnicity and ancestry consistent with epidemiologic observations in the Americas. The association remained significant after controlling for ancestry and income. No association was observed with markers in the gene encoding CD209 (DC-SIGN). An association between dengue hemorrhagic fever and JAK1 polymorphisms is in agreement with expression profiles showing generalized decreased type 1 interferon-stimulated gene expression in these patients.

Changes in hematological and serum biochemical parameters in common marmosets (Callithrix jacchus) after inoculation with dengue virus

“…hematological and biochemical parameters were, however, not detected in all of the DENV-inoculated marmosets. Although studies including larger number of animals are required, the results suggest that discrepancies in clinical signs and changes in parameters may in part be due to host factors such as genetic variation among individual marmosets, as has been observed in humans [21,[24][25][26][27][28][29][30][31][32]. In summary, the results provide data on changes in hematological and biochemical parameters, and clinical signs in common marmosets inoculated with DENV.…”

“…Marmosets D2-6 and D2-10, however, did not exhibit hematological changes. In addition to viral factors, host factors including immunological factors and genetic factors are speculated to have important implications on disease severity [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Seroepidemiological studies consistently support the role of immunological factors during secondary heterotypic infection as a risk factor for severe dengue.…”

Dengue severity associated with age and a new lineage of dengue virus‐type 2 during an outbreak in Rio De Janeiro, Brazil

“…Mechanisms that determine the variations in the clinical manifestations of dengue infections are not clearly understood, but are frequently associated with types of infection, viral serotype, genotype, lineages, and host genetic factors [Simmons et al, ]. The two most accepted hypotheses for the pathogenesis of dengue hemorrhagic fever (DHF) are based on antibody‐dependent‐enhancement or virulence of the viral strain [Halstead et al, ; Rosen, ; Rico‐Hesse et al, ; Silva et al, ]. According to the second hypothesis, disease severity depends on the degree of virulence of the DENV variants.…”

“…According to the second hypothesis, disease severity depends on the degree of virulence of the DENV variants. Therefore, strains that replicate more efficiently and reach higher serum titres have a greater epidemic potential and higher incidence of DHF and dengue shock syndrome [Rico‐Hesse et al, ; Vaughn et al, ; Rico‐Hesse, ; Silva et al, ].…”

Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population

“…Como contrapartida, el incremento sustancial de la propensión al dengue hemorrágico encontrada en la combinación alélica "AGC" ajustada por el componente amerindio, conjuntamente con su tendencia cuando no se ajustó (cuadro 5), apuntan a un efecto sobre la forma clínica del dengue, no solo de las variantes aquí estudiadas, sino que también sugiere la existencia de otras variantes de riesgo con origen amerindio que se deben continuar buscando, como lo han sugerido Silva, et al (47).…”