Tumor necrosis factor-alpha, transforming growth factor-β1, and interleukin-10 gene polymorphisms: implication in protection or susceptibility to dengue hemorrhagic fever.
Dengue virus infection has emerged as one of the most important arthropod-borne viral diseases. Some dengue infected individuals develop the severe, life-threatening form of the disease, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Host genetic factors may be relevant and may predispose some individuals to the severe illness. Human leukocyte antigen (HLA), FcγR, tumor necrosis factor (TNF)-α, and dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), among others genes have been associated with the pathogenesis of dengue. Little is known, however, about the predictive value of cytokine genotypes for the clinical outcome of dengue infection. In this study, the TNF-α, interleukin (IL)-6, interferon (IFN)-γ, IL-10 and transforming growth factor (TGF)-β1 gene single nucleotide polymorphisms (SNP) were studied by polymerase chain reaction-sequence-specific primer in a group of individuals with the antecedent of DHF during a secondary infection in the sequence dengue 1/dengue 2. A control group was also included. TNF-α (-308) A allele and IL-10 (-1082/-819/-592) ACC/ATA haplotype were significantly associated with DHF. TNF-α (-308) GG and TGF-β1 (c25) GG genotypes were associated with protection. Our results suggest that genetic predisposition to a high TNF-α production and a low IL-10 production seems to increase the susceptibility to DHF during a secondary dengue 2 infection, whereas TGF-β1 high producers might be protected for developing DHF.
Perez
Ana B
AB
PAHO/WHO Collaborating Center for the Study of Dengue and its Vector, Institute for Tropical Medicine Pedro Kouri, Havana, Cuba. anab@ipk.sld.cu
Sierra
Beatriz
B
Garcia
Gissel
G
Aguirre
Eglis
E
Babel
Nina
N
Alvarez
Mayling
M
Sanchez
Licel
L
Valdes
Luis
L
Volk
Hans D
HD
Guzman
Maria G
MG
D000328:Adult; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D019595:Severe Dengue / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D012769:Shock; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10