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 AB ，Sierra B ，Garcia G ，Aguirre E ，Babel N ，Alvarez M ，Sanchez L ，Valdes L ，Volk HD ，Guzman MG ... -  《-》

TNF-alpha-308A allele, a possible severity risk factor of hemorrhagic manifestation in dengue fever patients.

Fernández-Mestre MT ，Gendzekhadze K ，Rivas-Vetencourt P ，Layrisse Z ... -  《-》

Evidence for genetic susceptibility towards development of posttransplant lymphoproliferative disorder in solid organ recipients.

Babel N ，Vergopoulos A ，Trappe RU ，Oertel S ，Hammer MH ，Karaivanov S ，Schneider N ，Riess H ，Papp-Vary M ，Neuhaus R ，Gondek LP ，Volk HD ，Reinke P ... -  《TRANSPLANTATION》

Tumor necrosis factor alpha promoter polymorphisms in Mexican patients with dengue fever.

Increased levels of tumor necrosis factor alpha (TNF-α) in patients with dengue have been reported. Various polymorphisms have been identified in the promoter region of the TNF-α gene that may affect its transcription. The purpose of the present study was to evaluate the relationship between polymorphisms of TNF-α gene and the genetic susceptibility to dengue fever in a group of patients from Morelos State, Mexico. The TNF-α polymorphisms (positions -238 and -308) were determined by PCR-RFLP technique in 130 patients with dengue (85 with dengue fever and 45 with dengue hemorrhagic fever) and 169 healthy controls. The patients were selected from cases reported in Morelos State from 1997 to 2003. The whole group of dengue patients showed a decreased frequency of TNF-α -238 A allele when compared to healthy controls (p = 0.01, OR = 0.19, 95%CI = 0.02-0.78). When the analysis was made separately in dengue fever and dengue hemorrhagic fever patients, the decreased frequency of TNF-α -238 A allele only remained significant in patients with DHF when compared to healthy controls (p = 0.034). This work suggests a possible association of TNF-α -238 A allele with protection to develop symptomatic disease.

García-Trejo AR ，Falcón-Lezama JA ，Juárez-Palma L ，Granados J ，Zúñiga-Ramos J ，Rangel H ，Barquera R ，Vargas-Alarcón G ，Ramos C ... -  《-》

Polymorphisms in tumour necrosis factor-alpha, transforming growth factor-beta, interleukin-10, interleukin-6, interferon-gamma, and outcome of hepatitis C virus infection.

Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection (HCV), the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect response to therapy. Cytokine genes are polymorphic at specific sites, and certain mutations located within coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of this study was to investigate the frequency of genotypes associated with polymorphisms of TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma and to determine their association with the outcome of HCV infection. Genotyping was carried out by polymerase chain reaction sequence-specific primers on genomic DNA isolated from 158 individuals. Of these, 66 had spontaneously recovered from infection (persistently HCV RNA negative), while 92 had persistent infection (persistently HCV RNA positive). All patients were genotyped as high or low producers of TNF-alpha and IL-6 and high, intermediate, or low producers of TGF-beta, IL-10, and IFN-gamma based on single nucleotide substitutions. A significant proportion of patients with viral clearance were genotyped with a low IL-6 production profile, whereas those with persistent infection were genotyped with a high production profile (P = 0.02). No associations were observed between polymorphisms of TNF-alpha, IL-10, or IFN-gamma and viral clearance or persistent infection. Furthermore, there were no associations between cytokine genotypes and severity of disease. Inheritance of some genotypes associated with polymorphisms of cytokine genes, such as IL-6, may be host genetic factors associated with outcome of HCV in a well-defined ethnically homogeneous cohort.

Barrett S ，Collins M ，Kenny C ，Ryan E ，Keane CO ，Crowe J ... -  《JOURNAL OF MEDICAL VIROLOGY》