title: Polymorphisms of Transporter Associated with Antigen Presentation, Tumor Necrosis Factor-α and Interleukin-10 and their Implications for Protection and Susceptibility to Severe Forms of Dengue Fever in Patients in Sri Lanka.
abstract: BACKGROUND
  To date, a clear understanding of dengue disease pathogenesis remains elusive. Some infected individuals display no symptoms while others develop severe life-threatening forms of the disease. It is widely believed that host genetic factors influence dengue severity.
  
  
  OBJECTIVE
  This study evaluates the relationship between certain polymorphisms and dengue severity in Sri Lankan patients.
  
  
  METHODS
  Polymorphism studies are carried out on genes for; transporter associated with antigen presentation (TAP), promoter of tumor necrosis factor-α (TNF-α), and promoter of interleukin-10 (IL-10). In other populations, TAP1 (333), TAP2 (379), TNF-α (-308), and IL-10 (-1082, -819, -592) have been associated with dengue and a number of different diseases. Data have not been collected previously for these polymorphisms for dengue patients in Sri Lanka.
  
  
  METHODS
  The polymorphisms were typed by amplification refractory mutation system polymerase chain reaction in 107 dengue hemorrhagic fever (DHF) patients together with 62 healthy controls.
  
  
  METHODS
  Pearson's Chi-square contingency table analysis with Yates' correction.
  
  
  RESULTS
  Neither the TAP nor the IL-10 polymorphisms considered individually can define dengue disease outcome with regard to severity. However, the genotype combination, IL-10 (-592/-819/-1082) CCA/ATA was significantly associated with development of severe dengue in these patients, suggesting a risk factor to developing DHF. Also, identified is the genotype combination IL-10 (-592/-819/-1082) ATA/ATG which suggested a possibility for protection from DHF. The TNF-α (-308) GG genotype was also significantly associated with severe dengue, suggesting a significant risk factor.
  
  
  CONCLUSIONS
  The results reported here are specific to the Sri Lankan population. Comparisons with previous reports imply that data may vary from population to population.
authors.affiliation: Genetech Research Institute, Colombo 08, Sri Lanka.
authors.forename: Anira N
authors.initials: AN
authors.lastname: Fernando
authors.affiliation: Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka; MRC Human Immnology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
authors.forename: Gathsaurie Neelika
authors.initials: GN
authors.lastname: Malavige
authors.affiliation: Genetech Research Institute, Colombo 08, Sri Lanka.
authors.forename: Kuda Liyanage Nandika
authors.initials: KL
authors.lastname: Perera
authors.affiliation: Department of Zoology, Faculty of Science, University of Colombo, Sri Lanka.
authors.forename: Sunil
authors.initials: S
authors.lastname: Premawansa
authors.affiliation: MRC Human Immnology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Ogg
authors.affiliation: Genetech Research Institute, Colombo 08, Sri Lanka; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Aruna Dharshan
authors.initials: AD
authors.lastname: De Silva
keywords: Dengue; dengue hemorrhagic fever; interleukin-10; transporter associated with antigen presentation; tumor necrosis factor-α