|
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
Anira N Fernando1, Gathsaurie Neelika Malavige2, Kuda Liyanage Nandika Perera1, Sunil Premawansa3, Graham S Ogg4, Aruna Dharshan De Silva5
1 Genetech Research Institute, Colombo 08, Sri Lanka
2 Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka; MRC Human Immnology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK
3 Department of Zoology, Faculty of Science, University of Colombo, Sri Lanka
4 MRC Human Immnology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK
5 Genetech Research Institute, Colombo 08, Sri Lanka; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
Correspondence Address:
Aruna Dharshan De Silva
Genetech Research Institute, Colombo 08, Sri Lanka; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0974-777X.170501
|
|
Context: 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. Aims: This study evaluates the relationship between certain polymorphisms and dengue severity in Sri Lankan patients. Settings and Design: 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. Materials and 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. Statistical Analysis Used: 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. |
