Genetic Polymorphisms of Genes Innolved in Host immune Response to Dangue Severity in nepalese Population

Abstract

In dengue, endemic country like Nepal all four serotypes (DENV1-4) of dengue virus (DENV) is found to be prevalent causing dengue fever and its severe form dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The severity of the disease is determined by virus serotype, host immune and genetic status which if known, can help in early disease management. In South Asian countries DHF and DSS are noted as leading cause of child death. Study on the severity determining marker is being carried out in endemic areas in human sample, as there is no appropriate animal model mimicking the DHF/DSS as in human and it is one of the limitations. Genetic makeup of the individual differs from place to place around the world which might be the reason for one population being more susceptible and the other being resistant to the virus. If polymorphism behind the positive or negative association between the gene and disease pathogenesis is well defined, then it could help in development of new preventive and therapeutic agents against disease. The study is focused on the severity marker prediction which might help in early diagnosis of the severe dengue cases. Genetic Marker was detected by Single nucleotide polymorphism detection by amplification refractory mutation system PCR (ARMS) of DNA extracted from selected samples. Statistical analysis of the clinical parameters of all the case samples was performed to classify the samples in dengue hemorrhagic(DHF) 53%, severe dengue (DS) 14% and Dengue fever(DF) 33%. Serotyping by Real-time PCR and Nested PCR showed the cocirculation

of DENV 2 serotype of dengue in the year 2019. Single nucleotide polymorphism(SNP) of three different genes were identified using amplification refractory mutation system PCR using the allele specific primers for TNF  (+308 A/G - rs1800629), IFNG (+874A/T − rs2430561), Interleukin 10 (IL-10) (819 C/T and 1082 A/G). CT genotype of TNF-was observed in 60% of case population, in case of Interleukin 10 (IL-10) (819 C/T and 1082 A/G) CT and AG genotype was seen in most of the study population 71% and 62% respectively. For IFNG (+874A/T − rs2430561), AT (45%) genotype followed by AA (40%) whereas only 15% with TT genotype was reported. In case of FC RIIa, heterozygote genotype AG variant was detected in all study population. As the population size was small in this study, the role of SNPs in severity could not be exactly predicted but this study provides future insight in predicting the role of these biomarkers in susceptibility, progression or protection a disease Keywords: DENV, DHF, DS, Severity markers, Single Nucleotide Polymorphism, TNFIFNG, Interleukin 10