title: Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever.
abstract: 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.
authors: Dengue Group, National Institute of Virology, 20 A Dr. Ambedkar Road, Pune, Maharashtra, India. alagarasu@gmail.com
authors: K
authors: K
authors: Alagarasu
authors: A P
authors: AP
authors: Mulay
authors: R
authors: R
authors: Singh
authors: V B
authors: VB
authors: Gavade
authors: P S
authors: PS
authors: Shah
authors: D
authors: D
authors: Cecilia
mesh_terms: D000328:Adult; D000483:Alleles; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019595:Severe Dengue / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha