Correlation of an interleukin-4 gene polymorphism with susceptibility to severe enterovirus 71 infection in Chinese children.

Enterovirus 71 (EV71) has caused many outbreaks of diseases among children worldwide since it was first reported in 1974, but its mechanism of pathogenesis remains unclear. This study was designed to investigate the possible association of the IL-4 -589C/T gene polymorphism with severity of EV71 infection in Chinese children. The IL-4 -589C/T gene polymorphism was detected in EV71-infected subjects (n = 185), including those with mild cases (n = 102) and severe cases (n = 83) as well as healthy controls (n = 234), using an improved multiplex ligation detection reaction (iMLDR) technique. The plasma levels of IL-4 and IFN-γ were determined by enzyme-linked immunosorbent assays. The presence of the CC genotype (p = 0.022) and the C allele (OR, 2.1; 95 % CI, 1.3-3.6; p = 0.004) was significantly higher in severe cases. Furthermore, the CC genotype and C allele were also more frequently found in cases of EV71 encephalitis (p < 0.05). The plasma levels of IL-4 of the CC (7.9 ± 1.3 pg/mL, p < 0.001) and CT genotype (6.8 ± 2.1 pg/mL, p < 0.01) were significantly elevated compared to those of the TT genotype, but the plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower for the CC and CT genotypes than for the TT genotype (p < 0.05). These findings suggest that the IL-4 -589C allele could be a susceptibility factor in the development of EV71 disease in Chinese children.

Genetic polymorphism of CCL2-2510 and susceptibility to enterovirus 71 encephalitis in a Chinese population.

The study was performed in 36 Chinese patients with enterovirus 71 (EV71) encephalitis and 141 patients with EV71-related hand, foot and mouth disease (HFMD) without encephalitis. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism technique. Patients with EV71 encephalitis had a significantly higher frequency of the CCL2-2510GG genotypes when compared to patients with EV71-related HFMD without encephalitis (66.7% vs. 41.8%, p=0.028). The frequency of CCL2-2510G alleles was also significantly higher among the patients with EV71 encephalitis than among patients with EV71-related HFMD without encephalitis (79.2% vs. 64.9%, OR=2.1, 95% CI=1.1-3.8, P=0.023). Significant differences were found in gender, age, fever days, white blood cell count, C-reactive protein level, blood glucose concentration, and CCL2 level among genotypes of CCL2-2510A/G in EV71-infected patients, but no significant differences were found in alanine aminotransferase, aspartate aminotransferase, or creatine kinase myocardial isozyme levels or in cerebrospinal fluid evaluations (except monocytes) in patients with EV71 encephalitis. These findings suggest that the CCL2-2510G allele is associated with susceptibility to EV71 encephalitis in Chinese patients.

Genetic polymorphism of CCL2-2518, CXCL10-201, IL8+781 and susceptibility to severity of Enterovirus-71 infection in a Chinese population.

OBJECTIVE: The goal of this study was to examine the relationship between CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T gene polymorphism and severity of Enterovirus 71 (EV71) infection in a Chinese population. METHODS: A case-control study was conducted to compare the distribution of genotype and genetic frequency of the CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T gene polymorphisms among EV71-infected patients (n = 186), including mild cases (n = 103), severe cases (n = 83) and healthy control subjects (n = 233) with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and analyzed the relationship between the CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T gene polymorphism and the susceptibility to EV71 infection. RESULTS: No significant differences were found in the distribution of genotype CCL2-2518A/G, CXCL10-201A/G, and IL8+781C/T between the healthy control group and EV71-infected patients. However, three SNPs were associated with severity of EV71 infection: the G allele (genotypes AG or GG) in the CCL2-2518A/G (OR 2.34, 95 % CI 1.50-3.65, P < 0.001), the A allele (genotypes AA or AG) in the CXCL10-201A/G (OR 3.60, 95 % CI 1.73-7.47, P < 0.001), and the C allele (genotypes CC or CT) in the IL8+781C/T (OR 2.63, 95 % CI 1.67-4.13, P < 0.001) were more frequent in patients with severe EV71 infection. No significant difference was observed between EV71 encephalitis and severe cases. At the same time, there were significant differences in fever days, WBC, CRP and BG concentration, and CCL2, CXCL10 and IL-8 levels according to the three SNPs among 186 EV71-infected patients, but no significant differences were observed in gender, age, ALT, AST, CK-MB, and CSF evaluations. CONCLUSION: The G carrier of the CCL2-2518A/G, the A carrier of the CXCL10-201A/G, and the C carrier of the IL8+781C/T were found to be associated with severity of EV71 infection, and could be susceptibility factors in the development of EV71 infection in the Chinese population.

Impact of endothelial nitric oxide synthase gene polymorphism on severity of enterovirus 71-infection in Chinese children.

OBJECTIVES: Genetic polymorphism G894T on the endothelial nitric oxide synthase (eNOS) gene has been reported as a susceptibility factor in a number of diseases, but evidence of its effect on enterovirus 71 (EV71) infection is lacking. This study investigated the possible association between this polymorphism (rs1799983) and disease severity in Chinese children with EV71 infection. DESIGN AND METHODS: 185 children with EV71 infection (83 with severe and 102 with mild disease) and 234 control healthy children underwent testing with polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) to detect G894T polymorphism. In addition, plasma levels of nitric oxide (NO), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and serum eNOS activity were measured according to genotype. RESULTS: The presence of GT+TT genotypes and T allele were associated with severe cases compared to genotype GG (OR 2.5, 95% CI 1.2-5.3, P=0.017) and G (OR 2.4, 95% CI 1.2-4.8, P=0.011). Furthermore, in EV71 encephalitis, GT+TT genotype and T allele were also more frequent than GG and G (P<0.05). The NO level and eNOS activity in T carriers (GT+TT) (84.3±2.5µmol/L and 14.4±1.8U/mL) were significantly less compared to in G carriers (GG) (92.0±1.5µmol/L and 19.1±1.7U/mL, P<0.001). But T carriers had higher plasma levels of IL-1ß, IL-6, and TNF-α than people without a T allele (P<0.001), and a significant negative correlation was observed between NO and cytokine levels. CONCLUSION: The results indicate that carrying the T allele of the eNOS G894T gene polymorphism was associated with EV71 infection, and could be a susceptibility factor in the development of EV71 infection in Chinese children.

[Family-based association study of a variable number of tandem repeat polymorphism of DAT1 gene with Tourette syndrome in a Chinese Han population].

OBJECTIVE: To assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population. METHODS: A total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis. RESULTS: The repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481). CONCLUSION: Our data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.