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

• Main Authors: Anira N Fernando, Gathsaurie Neelika Malavige, Kuda Liyanage Nandika Perera, Sunil Premawansa, Graham S Ogg, Aruna Dharshan De Silva
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2015-01-01
• Series: Journal of Global Infectious Diseases
• Subjects: Dengue; dengue hemorrhagic fever; interleukin-10; transporter associated with antigen presentation; tumor necrosis factor-α
• Online Access: http://www.jgid.org/article.asp?issn=0974-777X;year=2015;volume=7;issue=4;spage=157;epage=164;aulast=Fernando

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.