Pro-inflammatory and anti-inflamatory cytokine genes polymorphisms and susceptibility to Japanese encephalitis disease in the North Indian population.

Abstract

Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in many regions of Asia. Cytokines, including pro-inflammatory and anti-inflammatory are key regulators playing a detrimental role in the host response to JE infection, pathogenesis and disease outcome. Evidently, the host's cytokine response is genetically determined, representing the complexity of interindividual differences regarding immune response to viral infection. The current study assesses the association of single nucleotide polymorphisms of classical interleukin IL-1β and IL-10 with JEV susceptibility and disease severity in north Indian population. We performed a case-control study using 85 JE patients and 85 healthy controls. Polymorphisms in the IL-1β (-511 C/T) and IL-10 (-1082 A/G) genes were genotyped using PCR-RFLP. All continuous variables were expressed as mean±standard deviation, and categorical variables were expressed in percentage. The mRNA level of IL-1β and IL-10 were found significantly increased in JE patients. In severe JE patients, IL-1β mRNA level was significantly higher with heterozygous (C/T) and homozygous (C/C) genotype compared to wild (T/T) genotype and mRNA level of IL-10 was higher in heterozygous genotype (A/G) compared to wild genotype (A/A). The C/T and C/C genotypes of IL-1β were significantly associated with higher risk of JE infection (p<0.05, OR=7.25 and 4.40) whereas, the A/G genotype of IL-10 was associated with a reduced risk of JEV infection (p<0.05, OR=0.30). The C allele of IL-1β was associated with fever and neck stiffness (p<0.05) and CT genotype was associated with disease severity and worse outcomes in JE patients. Along with this, IL-10 polymorphism was found associated with fever, and AG genotype was found to be associated with worse disease outcomes such as neurological sequelae (p<0.05). Mutant allele and genotype at IL-1β (-511 C/T) and IL-10 (-1082 A/G) gene polymorphism show increased expression of IL-1β and IL-10 in JE patients which contribute to disease severity as well as adverse outcomes of disease. Overall this is the first report from northern India, which shows the association of IL-1β and IL-10 polymorphisms with JEV infection.