RESUMEN
Enterovirus 71 (EV71) is a single-strand RNA virus that causes hand, foot and mouth disease (HFMD) in infants and young children, leading to neurological complications with significant morbidity and mortality. Unfortunately, the pathogenesis of EV71 infection is not well understood. In this study, we investigated the IL-17F rs1889570 and rs4715290 gene polymorphisms in a Chinese Han population. Severe cases and cases with EV71 encephalitis had a significantly higher frequency of the rs1889570 T/T genotype and T allele. The serum IL-17F levels in rs1889570 T/T and C/T genotypes were also significantly elevated when compared to C/C genotypes. However, there was no significant difference observed in rs4715290 genotype distribution and allele frequency. These findings suggest that IL-17F rs1889570 gene polymorphisms are significantly associated with the susceptibility to severe EV71 infection in Chinese Han children.
Asunto(s)
Enterovirus Humano A , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/epidemiología , Enfermedad de Boca, Mano y Pie/genética , Interleucina-17/genética , Polimorfismo de Nucleótido Simple , Pueblo Asiatico , Niño , Preescolar , Encefalitis Viral/epidemiología , Encefalitis Viral/etnología , Encefalitis Viral/genética , Encefalitis Viral/virología , Enterovirus Humano A/aislamiento & purificación , Enterovirus Humano A/patogenicidad , Femenino , Frecuencia de los Genes/genética , Genotipo , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Humanos , Interleucina-17/sangre , Masculino , Carga ViralRESUMEN
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.
Asunto(s)
Carnitina O-Palmitoiltransferasa/genética , Enterovirus Humano A , Infecciones por Enterovirus/genética , Adenosina Trifosfato/sangre , Pueblo Asiatico/genética , Preescolar , China , Susceptibilidad a Enfermedades/virología , Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/virología , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Índice de Severidad de la Enfermedad , Carga ViralRESUMEN
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.
Asunto(s)
Pueblo Asiatico/genética , Enterovirus Humano A/fisiología , Infecciones por Enterovirus/genética , Predisposición Genética a la Enfermedad , Interleucina-4/genética , Polimorfismo de Nucleótido Simple , Alelos , Niño , Preescolar , China , Enterovirus Humano A/genética , Infecciones por Enterovirus/sangre , Infecciones por Enterovirus/virología , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Interferón gamma/sangre , Interleucina-4/sangre , MasculinoRESUMEN
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.
Asunto(s)
Quimiocina CCL2/genética , Quimiocina CXCL10/genética , Infecciones por Enterovirus/genética , Predisposición Genética a la Enfermedad , Interleucina-8/genética , Pueblo Asiatico/genética , Quimiocina CCL2/sangre , Quimiocina CXCL10/sangre , Preescolar , Enterovirus Humano A , Infecciones por Enterovirus/sangre , Femenino , Humanos , Interleucina-8/sangre , Masculino , Polimorfismo de Nucleótido Simple , Índice de Severidad de la EnfermedadRESUMEN
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.
Asunto(s)
Quimiocina CCL2/genética , Encefalitis Viral/genética , Enterovirus Humano A/inmunología , Infecciones por Enterovirus/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Niño , Preescolar , China , Encefalitis Viral/inmunología , Infecciones por Enterovirus/inmunología , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Humanos , Lactante , Masculino , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
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.
Asunto(s)
Pueblo Asiatico/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Repeticiones de Minisatélite , Síndrome de Tourette/genética , Adolescente , Adulto , Pueblo Asiatico/etnología , Niño , Preescolar , Femenino , Humanos , Masculino , Linaje , Polimorfismo Genético , Síndrome de Tourette/etnología , Adulto JovenRESUMEN
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 ±.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.
Asunto(s)
Pueblo Asiatico/genética , Encefalitis Viral/genética , Enterovirus Humano A , Infecciones por Enterovirus/genética , Enfermedad de Boca, Mano y Pie/genética , Interleucina-6/genética , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Preescolar , Encefalitis Viral/diagnóstico , Encefalitis Viral/metabolismo , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/metabolismo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Enfermedad de Boca, Mano y Pie/diagnóstico , Enfermedad de Boca, Mano y Pie/metabolismo , Humanos , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Masculino , Polimorfismo Genético/genéticaRESUMEN
Enterovirus 71 (EV71) is one of the common pathogenic agents of hand, foot, and mouth disease (HFMD) and is associated with severe complications including encephalitis. Interleukin (IL)-17F plays an important role in tissue inflammation by inducing release of proinflammatory cytokines and chemokines. We investigated the association between EV71 encephalitis and of IL-17F 7488T/C (rs763780) gene polymorphism, which is known to cause a His-to-Arg substitution at amino acid 161. The study was performed in 58 Chinese patients with EV71 encephalitis and 127 Chinese patients with EV71-related HFMD without complications. Genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism technique. The patients with EV71 encephalitis had a significantly lower frequency of the IL-17F 7488TC+CC genotypes (10.3%) as compared to the patients with EV71-related HFMD without complications (27.6%, p = 0.008). The frequency of IL-17F 7488C alleles was also significantly lower among the patients with EV71 encephalitis (5.2%) as compared to that of the patients with EV71-related HFMD without complications (15%, OR = 0.310, 95% CI = 0.127-0.756, p = 0.006). Furthermore, homozygotes with the T allele had significantly higher levels of C-reactive protein, white blood cell count, and neutrophil count as compared to the patients with CC+CT genotypes (p = 0.004, 0.001, and 0.000, respectively). These findings suggested that the IL-17F 7488C allele could be significantly associated with protection against encephalitis in Chinese patients with EV71-related HFMD.
Asunto(s)
Encefalitis Viral/genética , Enterovirus Humano A , Infecciones por Enterovirus/genética , Enfermedad de Boca, Mano y Pie/virología , Interleucina-17/genética , Proteína C-Reactiva/análisis , Niño , Preescolar , China , Encefalitis Viral/complicaciones , Infecciones por Enterovirus/complicaciones , Femenino , Genotipo , Humanos , Lactante , Recuento de Leucocitos , Linfocitos/inmunología , Masculino , Monocitos/inmunología , Neutrófilos/inmunología , Polimorfismo GenéticoRESUMEN
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.