RESUMO
BACKGROUND: Most cases with anti-tuberculosis drug-induced hepatotoxicity (ATDH) have been attributed to isoniazid. OBJECTIVE: To evaluate whether the polymorphisms of the cytochrome P450 2EI (CYP2E1) and N-acetyltransferase 2 (NAT2) gene are associated with ATDH. DESIGN: A total of 140 tuberculosis (TB) patients without liver diseases before treatment who received anti-tuberculosis treatment were followed prospectively. Their CYP2E1 and NAT2 genotypes were determined using the TaqMan polymerase chain reaction assay. RESULTS: Forty-five (32.1%) patients were diagnosed with ATDH. No significant differences were reported in age and sex between patients with and without ATDH. Slow acetylators defined by NAT2 genotypes had a higher risk of hepatotoxicity than rapid acetylators (51.2% vs. 25.2%, P = 0.0026). Odds ratio (OR) analysis showed that slow acetylator status (OR 3.15, 95%CI 1.47-6.48) was the only independent risk factor for ATDH. Pyrazinamide co-administration induced hepatitis was also associated with NAT2 acetylator status. CYP2E1 c1/c1 homozygotes are prone to developing more severe hepatotoxicity than other c1/c2 and c2/c2 genotypes. CONCLUSION: The slow acetylator status of NAT2 is a significant susceptibility risk factor for ATDH. CYP2E1 is associated with the severity of ATDH.
Assuntos
Antituberculosos/efeitos adversos , Arilamina N-Acetiltransferase/genética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocromo P-450 CYP2E1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Estudos Prospectivos , Pirazinamida/efeitos adversos , Pirazinamida/uso terapêutico , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: The interleukin 17A (IL17A) gene, located on chromosome 6p and linked to asthma phenotype, is a highly potential candidate gene conferring asthma susceptibility. The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL17A and asthma in Taiwanese children. METHODS: We selected and performed genotyping on nine SNPs that encompass the genomic region of IL17A in Taiwanese children with or without asthma. A total of 1939 subjects containing 1027 subjects in testing group and 931 subjects in validation group were recruited in this study. RESULTS: After Bonferroni correction, SNP rs8193036 was found to have a weak association (P = 0.0074 x 9 = 0.066) in genotype frequency test. This association was confirmed by validation group. Logistic regression adjusted allergy comorbidity and gender showed a slightly weaker association. CONCLUSIONS: The results indicated an independent role of IL17A promoter polymorphism rs8193036 in the association with pediatric asthma in Taiwanese population.
Assuntos
Asma/genética , Predisposição Genética para Doença , Interleucina-17/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Asma/epidemiologia , Asma/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Interleucina-17/imunologia , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Taiwan/epidemiologiaRESUMO
MD-1 (myeloid differentiation 1; also known as Ly86, lymphocyte antigen 86), interacting with RP105, plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. It has been suggested to be involved in the pathological mechanism of inflammation and atopic diseases. The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of MD-1 promoter and coding region and mite-sensitive allergy in Taiwanese children. We conducted a case-control study on 237 controls and 281 allergic patients sensitive to Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) by genotyping 35 SNPs in MD-1 gene region. In the promoter region we identified three SNPs, rs1334710, rs4959389, and rs977785 that are associated with mite-sensitive allergy in Taiwanese children. The P-values ranged from 0.0150 to 0.009. The haplotypes including promoter region were also associated with mite-sensitive allergy. Our results suggested that MD-1 could be a susceptible gene for mite-sensitive allergy in Taiwanese children.
Assuntos
Antígenos de Dermatophagoides/imunologia , Antígenos de Superfície/genética , Haplótipos , Hipersensibilidade/genética , Imunoglobulina E/sangue , Polimorfismo de Nucleotídeo Único , Alérgenos/imunologia , Animais , Antígenos de Superfície/metabolismo , Estudos de Casos e Controles , Criança , Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Masculino , TaiwanRESUMO
Both surface treatments, H2-reducing pretreatment at 400 degrees C and the deposition of copper as a catalyst, were attempted to enhance the removal of nitrate (40 (mg N) L(-1)) using zerovalent iron in a HEPES buffered solution at a pH of between 6.5 and 7.5. After the iron surface was pretreated with hydrogen gas, the removal of the passive oxide layers that covered the iron was indicated by the decline in the oxygen fraction (energy dispersive X-ray analysis) and the overlap of the cyclic polarization curves. The reaction rate was doubled, and the lag of the early period disappeared. Then, the deposition of copper onto freshly pretreated iron promoted nitrate degradation more effectively than that onto a nonpretreated iron surface, because of the high dispersion and small size of the copper particles. An optimum of 0.25-0.5% (w/w) Cu/Fe accelerated the rate by more than six times that of the nonpretreated iron. The aged 0.5% (w/w) Cu/Fe with continual dipping in nitrate solution for 20 days completely restored its reactivity by a regeneration process with H2 reduction. Hence, these two iron surface treatments considerably promoted the removal of nitrate from near-neutral water; the reactivity of Cu/Fe was effectively recovered.