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 ... -  《-》

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 ... -  《-》

Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever.

Genes coding for human leukocyte antigen (HLA) class II molecules and tumor necrosis factor (TNF)-α are polymorphic and have been shown to influence susceptibility to infectious diseases. In the present study, HLA-DRB1, -DQB1 and TNF gene polymorphisms were investigated in 114 dengue patients (DEN) [85 dengue fever (DF) cases and 29 dengue hemorrhagic fever (DHF) cases] and 110 healthy controls (HCs) using PCR based methods. The frequencies of HLA-DRB1*07 allele [DF vs. DHF, P=0.0034, Pc=0.044, OR 3.79] and HLA-DRB1*07/*15 genotype [DF vs. DHF, P=0.00071, Pc=0.038, OR 10.41] were significantly higher in DHF cases as compared to HCs and DF cases. Higher frequency of rs1800629 'G/A' genotype was observed in DHF cases as compared to DF cases. The frequency of rs1799964 'C/C' genotype of the TNF gene was found to be significantly higher in all patient groups compared to HCs [HCs vs. DEN, P=0.0054, Pc=0.0162, OR 3.57; HCs vs. DF, P=0.036, OR 2.89; HCs vs. DHF, P=0.0088, Pc=0.0240, OR 5.11]. Presence of combination of HLA-DRB1*07/*15 with either rs1799964 'C/C' genotype or rs1800629 'G/A' genotype or both was present in 17.2% of DHF cases and 1.2% in HCs while this combination was not observed in DF cases. The results suggest that HLA-DRB1*07/*15 genotype in combination with TNF polymorphisms influence progression to DHF.

Alagarasu K ，Mulay AP ，Singh R ，Gavade VB ，Shah PS ，Cecilia D ... -  《-》

Tumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoid arthritis, and systemic lupus erythematosus in a Mexican pediatric population.

Jiménez-Morales S ，Velázquez-Cruz R ，Ramírez-Bello J ，Bonilla-González E ，Romero-Hidalgo S ，Escamilla-Guerrero G ，Cuevas F ，Espinosa-Rosales F ，Martínez-Aguilar NE ，Gómez-Vera J ，Baca V ，Orozco L ... -  《-》