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Introduction: This study was designed to explore the association between the TMEM173 polymorphism (rs7447927) and the severity of enterovirus 71 (EV71) infection among Chinese children. Methods: The TMEM173 polymorphism was identified in EV71‐infected patients (n = 497) and healthy controls (n = 535) using the improved multiplex ligation detection reaction (iMLDR). The interferon‐α (IFN‐α) serum levels were detected using enzyme linked immunosorbent assay (ELISA). Results: The frequencies of the GG genotype and G allele of TMEM173 rs7447927 in the mild EV71 infection and severe EV71 infection groups were markedly higher than those in the control group. The GG genotype and G allele frequencies in severely infected EV71 patients were significantly higher than those in mildly infected EV71 patients. Severely infected EV71 patients with the GG genotype had higher white blood cell counts (WBC), and C‐reactive proteins (CRP), and blood glucose (BG) levels, longer fever duration, higher vomiting frequency, spirit changes, and electroencephalography (EEG) abnormalities. IFN‐α serum concentration in severely infected patients was significantly higher than in the mildly infected group. The IFN‐α concentration in the GG genotype was significantly higher compared with those in the GC and CC genotypes in severe cases. Conclusions: The TMEM173 rs7447927 polymorphism was associated with EV71 infection susceptibility and severity. The G allele and GG genotype are susceptibility factors in the development of severe EV71 infection in Chinese children. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore the association between the IRAK4 polymorphism rs4251545 and the severity of enterovirus 71 (EV71) infection in Chinese children. Methods: We analyzed the IRAK4 polymorphism rs4251545 in 617 EV71‐infected patients and 410 controls using the improved multiplex ligation detection reaction. IRAK4 mRNA expression was tested by qRT‐PCR. Serum concentrations of IL‐6 and NF‐κB were detected using ELISA. Results: The frequencies of the GA + AA genotype and A allele in the mild EV71 infection group and in the severe EV71 infection group were significantly higher than those in the normal control group. The frequency of the GA + AA genotype and A allele in severely infected EV71 patients was markedly higher than that in mildly infected EV71 patients. IRAK4 mRNA expression in mildly infected EV71 patients and severely infected patients was significantly higher than that in the control group. IRAK4 mRNA expression in GA + AA genotypes in both mild and severe EV71 infection groups was significantly higher than that in patients with the GG genotype. IL‐6 concentration and the ratio of IL‐6/NF‐κB in severe EV71 cases were significantly lower in patients with the GA + AA genotype than in those with the GG genotype. The ratio of IL‐6/NF‐κB was distinctly higher in severely infected EV71 patients than in mildly infected and control subjects. Conclusions: The IRAK4 polymorphism rs4251545 was associated with the susceptibility and severity of EV71 infection. The A allele is a susceptible factor in the development of severe EV71 infection in Chinese children. [ABSTRACT FROM AUTHOR]

Background Oligoadenylate synthetase 3 (OAS3) is interferon-induced antiviral enzyme, playing a significant role in the innate immune response. Genetic polymorphism in OAS3 gene has been reported to be a susceptibility factor in many infected diseases, but evidence of its effect on enterovirus 71 (EV71) infection is still lacking. Objectives An attempt study was made to investigate whether genetic polymorphism of OAS3 S381R is associated with the severity of EV71 infection in Chinese children. Study design Retrospectively sumed up the clinical onsets and experimental results for 249 cases with EV71 infection (including 151 mild cases and 98 severe cases) and 243 controls. An improved multiplex ligation detection reaction (iMLDR) technique was carried out to analyze polymorphism in OAS3 S381R G/C gene for genetic association analyses. The plasma levels of IFN-γ were determined by enzyme-linked immunosorbent assays. Results The distribution of OAS3 S381R CC genotype (73.47%) and C allele (85.20%) in severe cases was markedly higher than in mild cases (45.70%, P < .01; 67.88%, P < .01). The blood IFN-γ levels of severe cases were significantly lower in CC genotype (131.66 ± 10.84 pg/mL) compared to GG (183.37 ± 24.50 pg/mL, p < .01) and GC genotype (168.48 ± 26.57 pg/mL, p < .01). Conclusions Carrying the C allele of the OAS3 S381R gene could be a susceptibility factor in the development of severe EV71 infection in Chinese children. [ABSTRACT FROM AUTHOR]

The 2'5'-oligoadenylate synthetase (OAS) is an interferon (IFN)-induced protein that plays an important role in the antiviral action of IFN, with OAS3 being one of the four OAS classes (OAS1, OAS2, OAS3, OASL). The effect of OAS on several infectious viral diseases has been reported; however, a study of the effect of OAS3 on enterovirus 71 (EV71) is lacking. The purpose of this study was to evaluate the association of the OAS3 rs1859330 G/A genetic polymorphism with susceptibility and severity of EV71 infection. We investigated 370 Chinese Han children with hand-foot-mouth disease (HFMD) (214 of which were mild cases while 156 were severe). An improved multiplex ligation detection reaction (iMLDR) technique was carried out to examine the genotype. The AA genotype distribution (p = 0.002) and A allele frequency (OR = 1.83, 95% CI 1.32-2.52, p < 0.001) of OAS3 rs1859330 in severe cases were significantly higher than in mild cases. When comparing the different genotypes in EV71-infected patients, there were statistical differences in relation to rash (p = 0.03), oral ulcers (p = 0.005), pathologic reflex (p = 0.003), WBC counts (p = 0.032), CRP (p = 0.024), BG concentrations (p = 0.029), ALT (p = 0.02), and EEG (p = 0.019). However, there were no differences in relation to age, gender, AST, CK-MB, CT/ MRI, as well as some symptoms and signs (e.g. duration of fever (days), headache, convulsions, consciousness disturbance, paralysis, sign of meningeal irritation). In the cerebrospinal fluid (CSF) of severe cases, there were no differences in the levels of white cells, protein, glucose, chloride, lymphocytes and monocytes between the different genotypes. The plasma levels of IFN-γ in EV71-infected patients were significantly higher than in the control group (p < 0.01). IFN-γ concentrations in severe cases were lower in A allele carriers (AA+GA) (118.5 ± 12.6pg/mL) than in GG homozygotes (152.6 ± 56.3pg/mL p < 0.05). These findings suggest that the OAS3 rs1859330 G/A genetic polymorphism is associated with the severity of EV-71 infection, and that the A allele is a risk factor for the development of severe EV71 infection. [ABSTRACT FROM AUTHOR]

Genetic polymorphism in the carnitine palmitoyl transferase 2 (CPT2) gene has been reported to be a susceptibility factor in a number of syndromes of acute encephalopathy with various infectious diseases, but evidence of its effect on enterovirus 71 (EV71) infection is lacking. The goal of this study was to examine the relationship between genetic polymorphism of CPT2 and severity of EV71 infection in a Chinese population. PCR of five exons of the CPT2 gene was carried out to identify single-nucleotide polymorphisms (SNPs) in EV71-infected subjects (n = 333), including mild cases (n = 271) and severe cases (n = 62) as well as healthy controls (n = 328). Blood ATP levels were measured within 24 h of admission. The frequency of the A allele of rs1799821 ( P = 0.023) and the G allele of rs2229291 ( P = 0.009) in the CPT2 gene was higher in patients with severe EV71 infection. The A-G haplotype of rs1799821and rs2229291 was directly linked to EV71 severe infection risk when compared to all other haplotypes (OR = 2.005, 95 % CI = 1.087-3.700, P = 0.024). The blood ATP levels of severe cases were significantly lower than in mild cases ( P < 0.01) and controls ( P < 0.01). A significant negative correlation was observed in haplotype A-G between ATP levels and physical findings in severe cases ( P < 0.05). These findings suggest that CPT2 polymorphism may be associated with severity of EV71 infection and that the A-G haplotype of the CPT2 gene is involved in the inflammatory process of EV71 infection. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6), as one of pro-inflammatory cytokines, plays a key role in Enterovirus 71 (EV71) encephalitis. We investigated the association of IL-6-572C/G polymorphism and serum or cerebrospinal fluid (CSF) IL-6 level with EV71 encephalitis in patients with hand, foot, and mouth disease (HFMD). This study was carried out in 59 Chinese Han patients with EV71 encephalitis, 128 EV71-related HFMD without complications, and 232 controls. The IL-6-572C/G polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism gene analysis. Serum or CSF IL-6 levels were determined using a commercial enzyme-linked immunosorbent assay. The patients with EV71 encephalitis had a higher frequency of IL-6-572GG/GC genotype compared to the patients with EV71-related HFMD without encephalitis complications (40.7 vs. 15.6 %, odds ratio (OR) = 3.70, 95 % confidence interval (CI) = 1.83-7.50, p = 0.001). Similarly, the frequency of IL-6-572 G allele among the patients with EV71 encephalitis was also higher than that of patients with EV71-related HFMD without encephalitis complications (23.7 vs. 8.6 %, OR = 3.31, 95 % CI = 1.80-6.08, p < 0.001). Serum IL-6 levels in G carries (CG + GG) (195.1 ± 11.8 pg/ml) elevated significantly compared to CC homozygotes (167.7 ± 6.7 pg/ml) in EV71-infected patients ( p < 0.001), but no significant differences were observed in CSF IL-6 levels among different genotypes in patients with EV71 encephalitis. Furthermore, G carriers (GG + GC) (10.6 ± 1.29 mg/l) had significantly higher blood CRP levels compared to CC homozygotes (9.31 ± 1.93 mg/l) in patients with EV71 encephalitis ( p = 0.005). These findings suggested that IL-6-572 G allele was significantly associated with the susceptibility to EV71 encephalitis in Chinese Han patients, and IL-6-572 G allele might elevate the risk to EV71 encephalitis. [ABSTRACT FROM AUTHOR]