RESUMEN
The aim of this study was to analyze the influence of nucleotide transition (G/A) in position -2518 of the MCP-1 gene related to the susceptibility of developing RA. Two hundred twenty-three consecutive RA patients according to 2010 ACR/EULAR criteria were included; 120 healthy subjects were used as controls. MCP-1 -2518 A/G polymorphism (AG + GG) was present in 162 (72.6 %) RA patients and in 63 (52.5 %) healthy subjects [OR 2.44 (IC95% 1.53-3.88, p = 0.0002)]; associations for heterozygotes and homozygotes were OR 1.92 (IC95% 1.19-3.15, p = 0.001) and OR 5.19 (IC95% 2.34-11.51, p = 0.001), respectively. In Argentine patients, MCP-1 gene polymorphism confers susceptibility for developing RA.
Asunto(s)
Artritis Reumatoide/genética , Quimiocina CCL2/genética , Polimorfismo Genético , Alelos , Argentina/epidemiología , Artritis Reumatoide/epidemiología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIM: Treatment with antituberculosis (TB) drugs produces liver damage in a large proportion of patients. Isoniazid, an antibacterial drug, is primarily responsible for this hepatotoxicity. Several polymorphisms of the N-acetyltransferase 2 (NAT-2) and cytochrome P450 2E1 enzymes, which are involved in the metabolism of isoniazid, may be directly associated with the development of hepatotoxicity. This study was designed to analyze the association between the NAT-2 and CYP2E1 polymorphisms with the development of anti-TB drug-induced hepatotoxicity (ATDH). METHODS: One hundred and seventy-five TB patients who had been treated with anti-TB drugs were studied. The allelic and genotypic frequency distributions of the NAT-2 and CYP2E1 enzymes were studied using polymerase chain reaction-restriction fragment length polymorphisms methodology. A binary logistic regression analysis was used to compare the results between TB patients with and without the development of hepatotoxicity. RESULTS: Having a slow acetylator status (odds ratio [OR] = 2.615; confidence interval [CI] = 1.264-5.411; P = 0.01), being female (OR = 2.734; CI = 1.325-5.639, P = 0.006), and having Bolivian ethnicity (OR = 2.711; CI = 1.307-6.625, P = 0.007) were found to be independent predictor variables for ATDH. CONCLUSIONS: This study showed that a patient's NAT-2 acetylator status, gender, and ethnic origin may be regarded as important risk factors for developing hepatotoxicity. Contrary to expectations, the CYP2E1 c1/c2 polymorphism did not show a significant association with hepatotoxicity in this study. Given the increases in TB cases and ATDH incidence levels, as well as the associated hospitalization costs, it may also be helpful to know patients' acetylator status prior to or at the beginning of the TB treatment regimen.
Asunto(s)
Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Acetilación , Adulto , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Antituberculosos/metabolismo , Argentina/epidemiología , Arilamina N-Acetiltransferasa/genética , Arilamina N-Acetiltransferasa/metabolismo , Bolivia/etnología , Enfermedad Hepática Inducida por Sustancias y Drogas/etnología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Distribución de Chi-Cuadrado , Estudios Transversales , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Etnicidad , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Fenotipo , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Adulto JovenRESUMEN
INTRODUCCION: En Argentina se reportan alrededor de 11.000 casos nuevos de tuberculosis (TB) por año. El tratamiento con drogas anti-TB produce daño hepático en una gran proporción de los pacientes, y la isoniacida (INH) es la principal inductora de hepatotoxicidad. Algunos polimorfismos de las enzimas NAT-2 y CYP2E1, involucradas en el metabolismo de INH, estarían directamente asociados con el desarrollo de hepatotoxicidad.OBJETIVO: Analizar la distribución de las variantes alélicas *4, *5, *6, *7 y *14 de NAT-2 y c1/c2 de CYP2E1 en población sana argentina y en pacientes con TB que concurren a hospitales públicos de la ciudad de Buenos Aires y estudiar su asociación con el desarrollo de la hepatotoxicidad.METODOS: Se estudiaron 152 pacientes con TB tratados con drogas anti-TB. La distribución de frecuencias alélicas y genotípicas fue determinada por PCR-RFLP, y los resultados fueron comparados entre pacientes con TB con o sin desarrollo de hepatotoxicidad, usando un análisis de regresión logística binaria.RESULTADOS: El estado acetilador lento resultó la única variable independiente en la predicción de hepatotoxicidad relacionada con las drogas anti-TB (p = 0,019; OR = 2,971).CONCLUSIONES: El presente estudio demuestra que, dada la alta prevalencia del estado acetilador lento en la población argentina y su asociación al riesgo de desarrollar hepatotoxicidad, junto con el aumento en los casos de TB y los costos que conllevan las internaciones por daño hepático asociado a drogas anti-TB, el análisis del estado acetilador previo al tratamiento anti-TB podría ser clave.
INTRODUCTION: In Argentina, about 11.000 new cases of tuberculosis (TB) are reported per year. Treatment with anti-TB drugs produces liver damage in a large proportion of patients, being isoniazid (INH) the main responsible for hepatotoxicity. Some polymorphisms of the enzymes NAT-2 and CYP2E1, which are involved in the metabolism of INH, might be directly associated with the development of hepatotoxicity.OBJECTIVE: To analyze the distribution of NAT-2 variants *4, *5, *6, *7 and *14, and CYP2E1 alleles c1 and c2 in a healthy population from Argentina and in patients with TB who attend public hospitals in Buenos Aires city, and to stude their association with the development of hepatotoxicity.METHODS: The study included 152 patients with TB treated with anti-TB drugs. The allelic and genotypic frequency distribution was determined by PCR-RFLP, and the results were compared between TB patients with or without development of hepatotoxicity using a binary logistic refression analysis.RESULTS: The slow acetylator status was the only independent variable in the prediction of hepatotoxicity associated with anti-TB drugs (p = 0.019; OR = 2.971).CONCLUSIONS: This study shows that, given the high prevalence of slow acetylator status in Argentine population and its association with the risk of hepatotoxicity, together with the increase in TB cases and the hospitalization costs due to liver damage associated with anti-TB drugas, the analysis of acetylator status before anti-TB treatment could be fundamental.
Asunto(s)
Tuberculosis , Antituberculosos , Citocromo P-450 CYP2E1 , Arilamina N-Acetiltransferasa , Isoniazida , Enfermedad Hepática Inducida por Sustancias y Drogas , Salud Pública , ArgentinaRESUMEN
INTRODUCCION: En Argentina se reportan alrededor de 11.000 casos nuevos de tuberculosis (TB) por año. El tratamiento con drogas anti-TB produce daño hepático en una gran proporción de los pacientes, y la isoniacida (INH) es la principal inductora de hepatotoxicidad. Algunos polimorfismos de las enzimas NAT-2 y CYP2E1, involucradas en el metabolismo de INH, estarían directamente asociados con el desarrollo de hepatotoxicidad.OBJETIVO: Analizar la distribución de las variantes alélicas *4, *5, *6, *7 y *14 de NAT-2 y c1/c2 de CYP2E1 en población sana argentina y en pacientes con TB que concurren a hospitales públicos de la ciudad de Buenos Aires y estudiar su asociación con el desarrollo de la hepatotoxicidad.METODOS: Se estudiaron 152 pacientes con TB tratados con drogas anti-TB. La distribución de frecuencias alélicas y genotípicas fue determinada por PCR-RFLP, y los resultados fueron comparados entre pacientes con TB con o sin desarrollo de hepatotoxicidad, usando un análisis de regresión logística binaria.RESULTADOS: El estado acetilador lento resultó la única variable independiente en la predicción de hepatotoxicidad relacionada con las drogas anti-TB (p = 0,019; OR = 2,971).CONCLUSIONES: El presente estudio demuestra que, dada la alta prevalencia del estado acetilador lento en la población argentina y su asociación al riesgo de desarrollar hepatotoxicidad, junto con el aumento en los casos de TB y los costos que conllevan las internaciones por daño hepático asociado a drogas anti-TB, el análisis del estado acetilador previo al tratamiento anti-TB podría ser clave.
INTRODUCTION: In Argentina, about 11.000 new cases of tuberculosis (TB) are reported per year. Treatment with anti-TB drugs produces liver damage in a large proportion of patients, being isoniazid (INH) the main responsible for hepatotoxicity. Some polymorphisms of the enzymes NAT-2 and CYP2E1, which are involved in the metabolism of INH, might be directly associated with the development of hepatotoxicity.OBJECTIVE: To analyze the distribution of NAT-2 variants *4, *5, *6, *7 and *14, and CYP2E1 alleles c1 and c2 in a healthy population from Argentina and in patients with TB who attend public hospitals in Buenos Aires city, and to stude their association with the development of hepatotoxicity.METHODS: The study included 152 patients with TB treated with anti-TB drugs. The allelic and genotypic frequency distribution was determined by PCR-RFLP, and the results were compared between TB patients with or without development of hepatotoxicity using a binary logistic refression analysis.RESULTS: The slow acetylator status was the only independent variable in the prediction of hepatotoxicity associated with anti-TB drugs (p = 0.019; OR = 2.971).CONCLUSIONS: This study shows that, given the high prevalence of slow acetylator status in Argentine population and its association with the risk of hepatotoxicity, together with the increase in TB cases and the hospitalization costs due to liver damage associated with anti-TB drugas, the analysis of acetylator status before anti-TB treatment could be fundamental.