title: Association of Toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in Chinese children.
abstract: 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.
authors.affiliation: Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China.
authors.forename: Hongfang
authors.identifier: http://orcid.org/0000-0002-6816-9000
authors.initials: H
authors.lastname: He
authors.affiliation: Medical Research Center, The Affiliated Hospital of Qingdao University Medical School, Qingdao, People's Republic of China.
authors.forename: Shihai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Liu
authors.affiliation: Pediatric Department of the Affiliated Hospital of Jining Medical University, Jining, 272000, People's Republic of China.
authors.forename: Qiu-Bo
authors.initials: QB
authors.lastname: Li
authors.affiliation: Department of Paediatrics, Zibo City Maternal and Child Health Hospital, Zibo, 255000, People's Republic of China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Tan
authors.affiliation: Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Pediatric Department of the Qingdao Women and Children Hospital, No. 6 Tongfu Road, Qingdao, 266003, Shandong, People's Republic of China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China.
authors.forename: Ye-Dan
authors.initials: YD
authors.lastname: Liu
authors.affiliation: Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China.
authors.forename: Cheng-Qing
authors.initials: CQ
authors.lastname: Yang
authors.affiliation: Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China. drchenzb001@163.com.
authors.forename: Zong-Bo
authors.initials: ZB
authors.lastname: Chen
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D029821:Enterovirus A, Human / Q000502:physiology*; D004769:Enterovirus Infections / Q000097:blood / Q000235:genetics* / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide; D051196:Toll-Like Receptor 3 / Q000235:genetics*
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D015847:Interleukin-4; D007371:Interferon-gamma