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

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.