| Objective:This study was conducted to detect the relationship between IL-6-572C/G and-174G/C gene polymorphism and the susceptibility to EV71 encephalitis, as well as to determine the impact of IL-6-572C/G and-174G/C gene polymorphism on IL-6 expression and the clinical findings in children with EV71-infected HFMD.Methods:From July to September in 2013, we recruited 187 patients diagnosed with EV71-infected HFMD. They were divided into two groups including EV71 encephalitis patients(n=59) and HFMD without complications patients(n=128) which showed no neurological complications.Healthy childrenof 232 who underwent a health examination in our hospital and with no history of HFMD were included as controls. Clinical baseline data and laboratory parameters were recorded. Genomic DNA was extracted from ethylene diamine tetraacetic acid(EDTA)-treated 2-ml sample of peripheral blood. The IL-6-572C/G polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism(PCR-RFLP) gene analysis. The IL-6 concentration in serum or CSF was determined using a commercial enzyme-linked immunosorbent assay kit.Results: 1.The patients with EV71 encephalitis had a higher frequency of IL-6-572GG/GC genotype compared to patients with EV71-related HFMD without complications(40.7 vs. 15.6 %, OR=3.70, 95 %CI=1.83–7.50, p=0.001). Similarly, the frequency of IL-6-572 G allele among the patients with EV71 encephalitiselevated significantly compared to patients with EV71-related HFMD without complications(23.7 vs. 8.6 %,OR=3.31, 95 % CI=1.80–6.08, p<0.001) 2. IL-6-174G/C gene polymorphism is not found in this group observed. 3. Serum IL-6 concentration(195.1±11.8 pg/ml) in G carriers(GC + GG) 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 serum IL-6 levels among different genotypes in controls. EV71-infected patients’ serum IL-6 concentrations were significantly higher than controls’. We also found that there were no significant differences in CSF IL-6 concen-trations among EV71 encephalitis patients with CG/GG genotype(217.1±25.4 pg/ml, n=10) compared to CC homozygotes(205.2±30.5 pg/ml, n=10). 4. The relationship between blood CRP concentration and IL-6-572C/G genotype showed the similar trend. Blood CRP levels in EV71-infected patients with G allele(GG + GC)(8.61±2.69 mg/l) elevated significantly compared to CC homozygotes(7.15±2.79mg/l)(p=0.003). Furthermore,carriers of G allele(GG + GC)(10.6±1.29 mg/l) had significantly higher levels of CRP compared to CC homozygotes(9.31±1.93 mg/l) in patients with EV71 encephalitis(p=0.005). 5. Carriers of G allele(GG + GC) had significantly higher levels of white blood cell(WBC) count(medianof 13.3×109/l) and blood glucose(BG) concentration(median of 10.4 mmol/l) as compared to CC homozygotes(medians of 7.8×109/l and 6.8 mmol/l; p<0.001 and p=0.006, respectively). The duration of fever in G carriers(GG + GC) was significantly longer than that in CC homozygotes(p<0.001). However, no significant differences were observed in gender, age, alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatine kinase-myocardial isozyme(CK-MB),and viral loads(p>0.05).Conclusion: 1. IL-6-572 C/G gene polymorphism is significantly associated with the susceptibility to EV71 encephalitis. 2. IL-6-572 G allele might elevate the risk to EV71 encephalitis. 3. IL-6 expression is directly upregulated in G allele of IL-6-572 loci and the increased serum level of IL-6 modulates the blood CRP level. 4. IL-6-174G/C gene polymorphism is not found in this group observed.Objective:This study was conducted to detect the relationship between TLR3-1377C/T gene polymorphism and the susceptibility to EV71 encephalitis, as well as to determine the impact of TLR3 level on the clinical findings in children with EV71-infected HFMD.Methods:From July to September in 2013, we recruited 187 patients diagnosed with EV71-infected HFMD. They were divided into two groups including EV71 encephalitis patients(n=59) and HFMD without complications patients(n=128) which showed no neurological complications.Healthy childrenof 232 who underwent a health examination in our hospital and with no history of HFMD were included as controls. Clinical baseline data and laboratory parameters were recorded. Genomic DNA was extracted from ethylene diamine tetraacetic acid(EDTA)-treated 2-ml sample of peripheral blood. The TLR3-1377C/T polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism(PCR-RFLP) gene analysis. The TLR3 concentration in serum was determined using a commercial enzyme-linked immunosorbent assay kit.Results: 1.The patients with EV71 encephalitis had a similar frequency of TLR3-1377C/T genotype and allele compared to patients with EV71-related HFMD without complications. 2. Serum TLR-3 concentration in EV71-infected patients elevated significantly compared to the normal controls(t=11.03;t=18.39). Serum TLR-3 concentration in EV71 encephalitis(26.75±4.23ng/ml)was lower significantly than that in EV71-related HFMD without complications(35.64±6.65ng/ml)( t=18.39,P<0.05). EV71 encephalitis patients’(212.3±7.1pg/ml) serum IL-6 concentrations were significantly higher than EV71-related HFMD without complications’(168.2±5.8pg/ml)(t=25.99,P<0.05). The viral loads in EV71 encephalitis patients(4.0±0.4 log10 copies/μl) were significantly higher than those in EV71-related HFMD patients without complications(3.2±0.5log10copies/μl)(t=7.376, P<0.05).3. Serum TLR-3 concentration in EV71-infected patients elevated significantly compared to the homologue group of age in the normal controls(<1year:EV71 encephalitis group vs control group,t=2.791, EV71-related HFMD patients without complications vs control group,t=6.66;≥1year:EV71 encephalitis group vs control group,t=7.288, EV71-related HFMD patients without complications vs control group,t=11.92).However, Serum TLR-3 concentration in EV71 encephalitis group lower significantly compared to the homologue group of age in EV71-related HFMD patients without complications(<1year:t=4.638;≥1year:t=2.315. We also found that, in EV71 encephalitis group, serum TLR-3 concentration in <1year old group is lower significantly than that in ≥1year old group. However, We found there were no significant differences in serum TLR-3 concentration among <1year and ≥ 1year old groups in EV71-related HFMD patients without complications and normal controls.Conclusion: 1. There were no significant relationship observed between TLR3-1377C/T gene polymorphism and the susceptibility to EV71 encephalitis. 2. The lower serum TLR-3 level might reduce the action of inhibition to virus replication,and furthur promote the development of EV71 encephalitis. 3. There was difference in ages about serum TLR-3 level in EV71 encephalitis patients. The shortage of serum TLR-3 expression in infant undergoing EV71 might be one important factor leading to EV71 encephalitis.
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