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

BACKGROUND: 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-1ß and IL-10 with JEV susceptibility and disease severity in north Indian population. METHODS: We performed a case-control study using 85 JE patients and 85 healthy controls. Polymorphisms in the IL-1ß (-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. RESULTS: The mRNA level of IL-1ß and IL-10 were found significantly increased in JE patients. In severe JE patients, IL-1ß 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-1ß 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-1ß 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). CONCLUSION: Mutant allele and genotype at IL-1ß (-511 C/T) and IL-10 (-1082 A/G) gene polymorphism show increased expression of IL-1ß 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-1ß and IL-10 polymorphisms with JEV infection.

Increased serum microRNA-29b expression and bad recovery in Japanese encephalitis virus infected patients; A new component to improve the disease recovery.

BACKGROUND: Japanese encephalitis virus (JEV) is a neurotropic mosquito-borne Flavivirus, mainly prevalent in Asia. It is the most important causative agent of acute viral encephalitis in humans. Recently, micro RNAs are discovered as a key regulator of inflammatory and immune responses in various diseases including neurological and viral infections. Thus, this study was proposed to check whether changes in cellular miRNA expression due to JE virus infection, can be detected in circulation which would be helpful in diagnosis and treatment. METHODS: miRNAs (miR-29b and miR-146a) were analyzed in the serum of JEV infected patients using quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: miR-146a was found significantly decreased (p = 0.0008) in JEV infected patients as compared to healthy controls whereas miR-29b was significantly increased (p = 0.001) in JEV patients recovered with neurological sequelae when compared to those recovered without sequelae. CONCLUSION: In conclusion, miRNA can be measured in serum. Studying microRNAs will provide novel information and help us to identify the components that can serve as biomarkers and can lead to new discovery in controlling disease recovery.

Association of ICAM-1 (K469E) and MCP-1-2518 A > G polymorphism with risk of Japanese encephalitis in North Indian population.

BACKGROUND: Japanese encephalitis virus (JEV) is most important cause of viral encephalitis worldwide. The pathogenesis of this is probably attributed to the host genetic makeup. Intercellular adhesion molecule-1 (ICAM-1) and monocytes chemoattractant protein-1 (MCP-1) play a vital role in host defense mechanism against flavivirus causing encephalitis. We assessed the possible genetic association between ICAM-1 (K469E) and MCP-1-2518 A > G polymorphisms and Japanese Encephalitis in North Indian population. METHODS: We studied ICAM-1(K469E) and MCP-1-2518 A > G polymorphisms with the help of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Expression of ICAM-1 and MCP-1 were determined at mRNA and protein levels in JE patients and healthy controls by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). RESULTS: Homozygous (E/E) genotype of ICAM-1 was associated with clinical severity (p = 0.015) and outcome (p = 0.04) of JE, whereas, heterozygous (A/G) genotype of MCP-1-2518 A > G was associated with outcome in JE patients (p = 0.01). Among severe cases of JE, a higher level of ICAM-1 was observed in patients with E allele (E/K + E/E) of ICAM-1 (K469E) than non-E allele (K/K). The level of MCP-1 was found significantly increased in JE patients with homozygous (G/G) genotype when compared to wild (A/A) genotype of MCP-1-2518 A > G (p = 0.03). CONCLUSION: ICAM-1 (K469E) and MCP-1-2518 A > G polymorphisms lead to increased level of ICAM-1 and MCP-1 in Japanese Encephalitis which may be associated with severity as well as an adverse outcome of the disease. ICAM-1 (K469E) polymorphism may affect host susceptibility to Japanese encephalitis in North Indian population.