Association of Toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in Chinese children

• Published in: Archives of virology 2017-06, Vol.162 (6), p.1717-1723
• Main Authors: He, Hongfang, Liu, Shihai, Liu, Pei-pei, Li, Qiu-bo, Tan, Yu-xia, Guo, Ya, Li, Fei, Wang, Yuan-yuan, Liu, Ye-dan, Yang, Cheng-qing, Chen, Zong-bo
• Format: Article
• Language: English
• Subjects: Alleles; Asian Continental Ancestry Group - genetics; Biomedical and Life Sciences; Biomedicine; Brief Report; Child; Child, Preschool; Children; China; Enterovirus A, Human - physiology; Enterovirus Infections - blood; Enterovirus Infections - genetics; Enterovirus Infections - virology; Female; Gene polymorphism; Genes; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Humans; Infant; Infections; Infectious Diseases; Interferon; Interferon-gamma - blood; Interleukin 4; Interleukin-4 - blood; Male; Medical Microbiology; Plasma levels; Polymorphism, Single Nucleotide; Serum levels; TLR3 protein; Toll-Like Receptor 3 - genetics; Toll-like receptors; Virology
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-017-3265-9

Enterovirus 71 (EV71) infection has become one of the major threats to children globally in recent years. Toll-like receptor 3 (TLR3) plays an essential role in host defense against EV71 infection. This study was designed to assess the possible association between the TLR3c.1377C/T polymorphism and disease severity in Chinese children with EV71 infection. The TLR3c.1377C/T gene polymorphism was identified in EV71-infected patients (n = 177), including mild cases (n = 99) and severe cases (n = 78) as well as healthy controls (n = 225), using improved multiplex ligation detection reaction (iMLDR) technology. Serum levels of IFN-γ and IL-4 were measured using enzyme-linked immunosorbent assays. The presence of the TT genotype ( p = 0.030) and the T allele (OR, 1.8; 95% CI, 1.2-2.8; p = 0.010) was significantly more frequent in severe cases. The plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower with the TT (102.0 ± 24.2 pg/mL, p < 0.01 and 14.2 ± 2.8, p < 0.001) and CT genotypes (114.1 ± 26.2 pg/mL, p < 0.05 and 18.0 ± 3.1, p < 0.001) than with the CC genotype (135.5 ± 36.8 pg/mL and 24.9 ± 4.7), but the plasma levels of IL-4 with the TT (7.3 ± 1.7 pg/mL, p < 0.01) and CT genotypes (6.4 ± 1.3 pg/mL, p < 0.05) were significantly higher than with the CC genotype (5.5 ±1.3 pg/mL). These findings suggest that the TLR3c.1377T allele is associated with susceptibility to severe EV71 infection in Chinese children.