Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India.
Department of Biochemistry, Era's Lucknow Medical College and Hospital, Lucknow 226003, Uttar Pradesh, India.
Cytokine. 2022 Jan;149:155716. doi: 10.1016/j.cyto.2021.155716. Epub 2021 Oct 9.
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.
日本脑炎病毒（JEV）是亚洲许多地区病毒性脑炎的主要病因。细胞因子，包括促炎和抗炎细胞因子，是在宿主对 JE 感染、发病机制和疾病结局的反应中起关键调节作用的关键调节剂。显然，宿主的细胞因子反应是由遗传决定的，这代表了对病毒感染的免疫反应个体间差异的复杂性。本研究评估了经典白细胞介素 IL-1β 和 IL-10 的单核苷酸多态性与印度北部人群 JEV 易感性和疾病严重程度的关系。
我们使用 85 例 JE 患者和 85 名健康对照进行了病例对照研究。使用 PCR-RFLP 对 IL-1β（-511 C/T）和 IL-10（-1082 A/G）基因的多态性进行了基因分型。所有连续变量均表示为均数±标准差，分类变量表示为百分比。
在 JE 患者中发现 IL-1β 和 IL-10 的 mRNA 水平显著升高。在重症 JE 患者中，杂合子（C/T）和纯合子（C/C）基因型的 IL-1β mRNA 水平明显高于野生型（T/T）基因型，而 IL-10 的 mRNA 水平在杂合子基因型（A/G）中高于野生型基因型（A/A）。IL-1β 的 C/T 和 C/C 基因型与 JE 感染的风险显著增加相关（p<0.05，OR=7.25 和 4.40），而 IL-10 的 A/G 基因型与 JEV 感染的风险降低相关（p<0.05，OR=0.30）。IL-1β 的 C 等位基因与发热和颈强直相关（p<0.05），CT 基因型与 JE 患者的疾病严重程度和不良结局相关。此外，还发现 IL-10 多态性与发热有关，AG 基因型与神经后遗症等不良疾病结局有关（p<0.05）。
IL-1β（-511 C/T）和 IL-10（-1082 A/G）基因多态性的突变等位基因和基因型在 JE 患者中表现出 IL-1β 和 IL-10 的高表达，这有助于疾病的严重程度以及疾病的不良结局。总的来说，这是印度北部的首次报道，表明 IL-1β 和 IL-10 多态性与 JEV 感染有关。
