RESUMEN
El consumo crónico de alcohol en Uruguay es un problema creciente, sin embargo, las determinaciones de biomarcadores consensuados no se realizan sistemáticamente ni se investigan otros marcadores potenciales. Para validar la hipótesis de que las metaloproteinasas de matriz con actividad gelatinasa son biomarcadores de consumo crónico de alcohol, se evaluaron muestras de sangre de 100 alcohólicos que comenzaron a atenderse en la Unidad de Trastornos Relacionados con el Alcohol y de 50 donantes sanos no alcohólicos. Las muestras de alcohólicos presentaron actividad de gelatinasas que triplicaron la de los controles y aumentos pequeños pero significativos en los niveles de γ-glutamil transferasa, aspartato-aminotransferasa y volumen corpuscular medio. Los valores de transferrina deficiente en carbohidratos fueron menores en alcohólicos que en controles. Estos resultados permiten proponer a las gelatinasas como los indicadores más sensibles del consumo sostenido de alcohol en la población analizada, ya que las enzimas hepáticas y el volumen corpuscular medio muestran una tendencia acorde con la literatura pero no alcanzaron valores asociados a la patología. Dado que la transferrina deficiente en carbohidratos es considerada el biomarcador indirecto más sensible y específico de consumo crónico de alcohol, los valores menores obtenidos en alcohólicos respecto de controles sugieren problemas metodológicos que podrían subsanarse aplicando otras técnicas de medida o por la presencia de interferencias que deben ser identificadas. Finalmente, estos hallazgos justifican una extensión de este trabajo piloto, así como estudios adicionales centrados en la participación de las metaloproteinasas de matriz con actividad gelatinasa en las cascadas de daño asociadas al consumo crónico de alcohol.
Chronic alcohol consumption in Uruguay is a growing problem, however, determinations of consensual biomarker are not performed systematically neither potential markers are explored. To validate the hypothesis that matrix metalloproteinases with gelatinase activity are biomarkers of chronic alcohol consumption, blood samples of 100 alcoholics that began medical treatment at the Unidad de Trastornos Relacionados con el Alcohol and 50 healthy non-alcoholic donors were evaluated. Alcoholic samples showed gelatinase activity that tripled that of controls and small but significant increases in levels of γ-glutamyl transferase, aspartate-aminotransferase and mean cellular volume. Carbohydrate deficient transferrin values were lower in alcoholics than in controls. These results allow proposing gelatinases as the most sensitive indicators of sustained alcohol consumption in the population analyzed since hepatic enzymes and mean cellular volume showed a tendency consistent with the literature but did not reach values associated with the pathology. Since carbohydrate-deficient transferrin is considered the most sensitive and specific indirect biomarker of chronic alcohol consumption, lower values in alcoholics related to controls suggest methodological problems that could be solved by applying other measurement techniques or by the presence of yet unknown interferences. Finally, these findings justify an extension of this pilot work, as well as additional studies focused on the participation of matrix metalloproteinases with gelatinase activity in the cascades of damage associated with chronic alcohol consumption.
O consumo crônico de álcool no Uruguai é um problema crescente, no entanto, as determinações consensuais de biomarcadores não são realizadas sistematicamente ou os potenciais marcadores são explorados. Para validar a hipótese de que as metaloproteinases de matriz com atividade gelatinase são biomarcadores do consumo crônico de álcool, foram avaliadas amostras de sangue cd 100 alcoólatras que começaram a ser tratadas na Unidad de Trastornos Relacionados con el Alcohol e 50 doadores não-alcoólatras saudáveis. As amostras alcoólicas apresentaram atividade de gelatinase que triplicou a dos controles e pequenos más significativos aumentos nos níveis de γ-glutamil transferase, aspartato-aminotransferase e volume médio celular. Os valores de transferrina deficientes em carboidratos foram menores nos alcoolistas que nos controles. Esses resultados permitem que as gelatinases sejam propostas como os indicadores mais sensíveis do consumo sustentado de álcool na população analisada, uma vez que as enzimas hepáticas e o volume celular médio apresentam uma tendência consistente com a literatura, mas não alcançaram valores associados à patologia. Como a transferrina deficiente em carboidratos é considerada o biomarcador indireto mais sensível e específico do consumo crônico de álcool, os valores mais baixos em alcoólatras do que em controles sugerem problemas metodológicos que poderiam ser sanados pela aplicação de outras técnicas de mensuração pela presença de interferências que deben ser identificadas. Finalmente, esses achados justificam uma extensão deste trabalho piloto, bem como estudos adicionais voltados para a participação de metaloproteinases de matriz com atividade de gelatinase nas cascatas de danos associados ao consumo crônico de álcool.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Alcoholismo/diagnóstico , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Método Doble Ciego , Estudios Transversales , Estudios de Cohortes , Sensibilidad y Especificidad , Alcoholismo/enzimología , Alcoholismo/sangre , Índices de Eritrocitos , gamma-Glutamiltransferasa/sangreRESUMEN
BACKGROUND: Hazardous drinking (HD) is a serious health problem in people infected with human immunodeficiency virus type 1 (HIV-1). Single nucleotide polymorphisms (SNPs) in alcohol dehydrogenase (ADH) genes have been associated with HD in different populations, but there were no data about this in HIV-1-positive individuals. This study investigated the association of 4 nonsynonymous SNPs in ADH genes (Arg48His and Arg370Cys in ADH1B gene; Arg272Gln and Ile350Val in ADH1C gene) with HD in people living with HIV-1. METHODS: This case-control study included 365 HIV-1-positive individuals (121 with HD and 244 without HD). Sociodemographic variables were collected with a standardized individual questionnaire. HD (score ≥8) and binge drinking (BD) (drinks on the same occasion ≥5) were detected with the Alcohol Use Disorders Identification Test. The 4 SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. The Bonferroni correction was used (considering the 4 SNPs studied). RESULTS: There were no significant differences in the frequencies of Arg370Cys, Arg272Gln, and Ile350Val polymorphisms between HD cases and controls. Otherwise, Arg/His genotype (rs1229984) in ADH1B gene showed a protective effect against HD (aOR = 0.36; 95% CI: 0.14 to 0.90) and BD (aOR = 0.49; 95% CI: 0.21 to 0.95). Nevertheless, these differences were no longer significant after Bonferroni correction. CONCLUSIONS: The results of this study suggest a possible effect of the Arg48His genotype on the protection against HD in HIV-1-positive individuals.
Asunto(s)
Alcohol Deshidrogenasa/genética , Alcoholismo/genética , Estudios de Asociación Genética/métodos , VIH-1/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Alcoholismo/diagnóstico , Alcoholismo/enzimología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Alcoholism is a psychiatric disorder that composes one of the principal causes of health disabilities in the world population. Furthermore, the available pharmacotherapy is limited. Therefore, this research was carried out to better understand the basis of the underlying neurobiological processes of this disorder and to discover potential therapeutic targets. Real-time PCR analysis was performed in the amygdala nuclei region of the brain of mice exposed to a chronic three-bottle free-choice model (water, 5 and 10% v/v ethanol). Based on individual ethanol intake, the mice were classified into three groups: "compulsive-like" (i.e., ethanol intake not affected by quinine adulteration), "ethanol-preferring" and "ethanol non-preferring". A fourth group had access only to tap water (control group). The candidate gene ACSS2 was genotyped in human alcoholics by real-time polymerase chain reaction using the markers rs6088638 and rs7266550. Seven genes were picked out (Acss2, Acss3, Acat1, Acsl1, Acaa2, Hadh, and Hadhb) and the mRNA level of the Acss2 gene was increased only in the "compulsive-like" group (p = 0.004). The allele frequency of rs6088638 for the gene ACSS2 was higher in the Alcoholic human group (p = 0.03), although sample size was very small. The gene ACSS2 is associated with alcoholism, suggesting that biochemical pathways where it participates may have a role in the biological mechanisms susceptible to the ethanol effects.
Asunto(s)
Acetato CoA Ligasa/genética , Acetato CoA Ligasa/metabolismo , Alcoholismo/enzimología , Alcoholismo/genética , Adulto , Animales , Depresores del Sistema Nervioso Central/administración & dosificación , Conducta de Elección/fisiología , Conducta Compulsiva/enzimología , Conducta Compulsiva/genética , Modelos Animales de Enfermedad , Etanol/administración & dosificación , Femenino , Frecuencia de los Genes , Humanos , Masculino , Ratones , Polimorfismo de Nucleótido Simple , ARN Mensajero/metabolismoRESUMEN
El alcoholismo es un importante problema de salud pública. En los últimos años ha causado interés el metabolismo del alcohol, puesto que ha sido considerado un posible determinante biológico en la conducta de consumo. Variados estudios se han orientado a la búsqueda y comprensión de la influencia de polimorfismos, en genes que codifican para los principales sistemas enzimáticos que intervienen en el metabolismo hepático. El polimorfismo rs671 del gen que codifica la enzima ALDH2 ha sido asociado a un menor consumo de alcohol debido a la acumulación de acetaldehído en sangre. Diversos estudios indican que este polimorfismo es frecuente en países asiáticos y se considera un factor protector en los individuos que lo portan. Se incluyeron 207 individuos adultos no relacionados, a los cuales se les aplicó un cuestionario sobre consumo de alcohol. El polimorfismo rs671 fue analizado por la reacción de la polimerasa en cadena (PCR) seguida de restricción enzimática. Además, se determinaron los biomarcadores clásicos indirectos de consumo de alcohol, mediante técnicas enzimáticas y hematológicas. La frecuencia del genotipo homocigoto mutado AA para el polimorfismo rs671 fue 3,0% en sujetos consumidores de alcohol y 2,8% en el grupo no consumidor. La distribución de genotipos y las frecuencias alélicas para esta variante fueron semejantes entre los sujetos estudiados (p>0,05). Estos hallazgos sugieren que la variante rs671 del gen ALDH2 no está asociada al oconsumo de alcohol en los individuos estudiados.
Alcoholism is an important public health problem. In recent years, alcohol metabolism caused interest, since it has been considered a possible biological determinant of alcohol consumption behavior. Several studies have focused on finding and understanding the influence of polymorphisms affecting genes that encode for enzymatic systems involved in the hepatic metabolism. The rs671 polymorphism of the gene encoding ALDH2 has been associated with lower alcohol consumption by leading to acetaldehyde accumulation in blood. This genetic variant is frequently found in Asian population and has been considered as protector factor of alcoholism in these individuals. In the present study, 207 unrelated-adult individuals were included. Alcohol consumption was recorded using a structured questionnaire. The rs671 polymorphism was analyzed using polymerase chain reaction followed by enzymatic digestion. Furthermore, classical biomarkers for alcohol consumption were assessed using enzymatic and hematological techniques. The frequency of homozygote genotype for the A allele (AA) was 3 and 2.8% in those subjects defined as alcohol drinkers and non-alcohol drinkers respectively. The genotypes distribution and allelic frequencies were similar among the studied subject (p>0.05). These data suggest that rs671 ALDH2 gene polymorphism is not associated to alcohol consumption in the studied population.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Polimorfismo de Nucleótido Simple , Alcoholismo/genética , Aldehído Deshidrogenasa/genética , Polimorfismo Genético , Marcadores Genéticos , Chile , Reacción en Cadena de la Polimerasa , Encuestas y Cuestionarios , Alcoholismo/enzimología , Alcoholismo/psicología , Aldehído Deshidrogenasa/metabolismoRESUMEN
The purpose of this study was to investigate the longitudinal effect of marijuana and heavy alcohol use on the productivity status of nonmetropolitan African American young adults. This analysis was based on secondary data from the Family and Community Health Study. For alcohol, the study evaluated the effects on productivity status for individuals with heavy alcohol use trajectories from adolescence into young adulthood while marijuana effects were evaluated during the period when adolescents are more likely to have initiated usage (14-16 years of age). Productivity status was measured when study participants were between 18 and 21 years, for both alcohol and marijuana. Multivariate logistic regression models were used to test the association between subjects' drug use and productivity. Bivariate analysis of the effects of marijuana use indicate that marijuana users by age 16 are 35% less likely to be productive at age 21 than those who have not initiated marijuana use (p < .005). After controlling for individual, community, and family factors, the multivariate logistic models for alcohol and marijuana use suggest that early adolescence drug use (marijuana and heavy alcohol use) do not have an impact on productivity status during early adulthood. Analyzing and understanding the different drug use trajectories in relation to a productivity outcome is important for policies and research geared to preventing drug use and in identifying its relation with micro- and macro-level labor market outcomes.
Asunto(s)
Alcoholismo/enzimología , Negro o Afroamericano/estadística & datos numéricos , Eficiencia , Abuso de Marihuana/etnología , Adolescente , Consumo de Bebidas Alcohólicas/etnología , Niño , Femenino , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Fumar Marihuana/etnología , Características de la Residencia , Factores de Riesgo , Factores Socioeconómicos , Adulto JovenRESUMEN
This account of recent work presented at the 4th International Symposium on Alcohol Pancreatitis and Cirrhosis reports animal studies aimed at determining the role of the "acetaldehyde burst," generated shortly upon ethanol intake, as the mechanism of protection against alcoholism conferred by the ADH1B*2 polymorphism. Literature studies discussed suggest an additional role of the acetaldehyde burst on the paradoxical (hormesis) protection of the ADH1B*2 polymorphism against esophageal cancers in alcoholics.
Asunto(s)
Acetaldehído , Alcohol Deshidrogenasa/genética , Alcoholismo/genética , Neoplasias Esofágicas/genética , Estallido Respiratorio/genética , Acetaldehído/metabolismo , Alcohol Deshidrogenasa/metabolismo , Consumo de Bebidas Alcohólicas/genética , Consumo de Bebidas Alcohólicas/metabolismo , Alcoholismo/enzimología , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Animales , Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/prevención & control , Humanos , Polimorfismo Genético/genéticaRESUMEN
Alcohol dependence poses a serious medical and sociological problem. It is influenced by multiple environmental and genetic factors, which may determine differences in alcohol metabolism. Genetic polymorphism of the enzymes involved in alcohol metabolism is highly ethnically and race dependent. The purpose of this study was to investigate the differences, if present, in the allele and genotype frequency of alcohol dehydrogenase 1B (ADH1B), ADH1C and the microsomal ethanol-oxidizing system (MEOS/CYP2E1) between alcohol-dependent individuals and controls and also to determine if these genotypes cause a difference in the age at which the patients become alcohol dependent. The allele and genotype frequencies of ADH1B, ADH1C, and CYP2E1 were determined in 204 alcohol dependent men and 172 healthy volunteers who do not drink alcohol (control group). Genotyping was performed by PCR-RFLP methods on white cell DNA. ADH1B*1 (99.3%) and ADH1C*1 (62.5%) alleles and ADH1B*1/*1 (N = 201) and ADH1C*1/*1 (N = 85) genotypes were statistically more frequent among alcohol-dependent subjects than among controls (99.3 and 62.5%, N = 201 and 85 vs 94.5 and 40.7%, N = 153 and 32, respectively). Differences in the CYP2E1 allele and genotype distribution between groups were not significant. The persons with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes became alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes (28.08, 25.67 years vs 36.0, 45.05, 34.45 years, respectively). In the Polish men examined, ADH1C*1 and ADH1B*1 alleles and ADH1C*1/*1 and ADH1B*1/*1 genotypes favor alcohol dependence. The ADH1B*2 allele may protect from alcohol dependence. However, subjects with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes become alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes.
Asunto(s)
Alcohol Deshidrogenasa/genética , Alcoholismo/enzimología , Citocromo P-450 CYP2E1/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Factores de Edad , Anciano , Alcoholismo/genética , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polonia , Adulto JovenRESUMEN
Alcohol dependence poses a serious medical and sociological problem. It is influenced by multiple environmental and genetic factors, which may determine differences in alcohol metabolism. Genetic polymorphism of the enzymes involved in alcohol metabolism is highly ethnically and race dependent. The purpose of this study was to investigate the differences, if present, in the allele and genotype frequency of alcohol dehydrogenase 1B (ADH1B), ADH1C and the microsomal ethanol-oxidizing system (MEOS/CYP2E1) between alcohol-dependent individuals and controls and also to determine if these genotypes cause a difference in the age at which the patients become alcohol dependent. The allele and genotype frequencies of ADH1B, ADH1C, and CYP2E1 were determined in 204 alcohol dependent men and 172 healthy volunteers who do not drink alcohol (control group). Genotyping was performed by PCR-RFLP methods on white cell DNA. ADH1B*1 (99.3 percent) and ADH1C*1 (62.5 percent) alleles and ADH1B*1/*1 (N = 201) and ADH1C*1/*1 (N = 85) genotypes were statistically more frequent among alcohol-dependent subjects than among controls (99.3 and 62.5 percent, N = 201 and 85 vs 94.5 and 40.7 percent, N = 153 and 32, respectively). Differences in the CYP2E1 allele and genotype distribution between groups were not significant. The persons with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes became alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes (28.08, 25.67 years vs 36.0, 45.05, 34.45 years, respectively). In the Polish men examined, ADH1C*1 and ADH1B*1 alleles and ADH1C*1/*1 and ADH1B*1/*1 genotypes favor alcohol dependence. The ADH1B*2 allele may protect from alcohol dependence. However, subjects with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes become alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes.
Asunto(s)
Adolescente , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Alcohol Deshidrogenasa/genética , Alcoholismo/enzimología , /genética , Polimorfismo Genético/genética , Factores de Edad , Alcoholismo/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Frecuencia de los Genes/genética , Polonia , Adulto JovenRESUMEN
BACKGROUND: Alcohol abuse represents the major identified etiological factor of cirrhosis in México. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out. METHODS: One hundred and one HUI and 331 MES subjects were studied. Genotype and allele frequency were assessed through polymerase chain reaction-restriction fragment length polymorphism after DNA isolation from peripheral leukocytes. Commercial kits for lipid and hepatic determinations were used. RESULTS: Polymorphic allele distribution in HUI was: 0%ADH1B*2, 0.5%ALDH2*2, 51.5%CYP2E1*c2; in MES: 3.4%ADH1B*2, 0%ALDH2*2, 16.1%CYP2E1*c2. Frequency of ADH1B*2 was statistically (p < 0.001) lower in HUI than MES. CYP2E1*c2 polymorphic allele was significantly higher (p < 0.0001) in HUI than MES. Hepatic profile was normal in both groups. HUI showed a better lipid profile than MES independently of genotype. CONCLUSIONS: Huichols exhibited the highest CYP2E1*c2 allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and ALDH2*2 were practically absent. This feature could be useful in the understanding of Mexican population gene composition, alcohol metabolism, and alcoholic liver disease development. However, further association studies are necessary. The heterogeneity of Mexican population was evidenced by the significantly different distribution of CYP2E1*c2 allele observed among different regions of the country. Lipid and hepatic values were not associated to genotype. This report constitutes the first study dealing with gene polymorphisms of alcohol metabolizing enzymes conducted in HUI.
Asunto(s)
Alcoholismo/enzimología , Alcoholismo/genética , Alelos , Citocromo P-450 CYP2E1/genética , Polimorfismo Genético/genética , Grupos de Población/genética , Adulto , Anciano , Alcoholismo/etnología , Femenino , Frecuencia de los Genes/genética , Humanos , Masculino , México/etnología , Persona de Mediana Edad , Grupos de Población/etnología , Adulto JovenRESUMEN
Humans who carry a point mutation in the gene coding for alcohol dehydrogenase-1B (ADH1B*2; Arg47His) are markedly protected against alcoholism. Although this mutation results in a 100-fold increase in enzyme activity, it has not been reported to cause higher levels of acetaldehyde, a metabolite of ethanol known to deter alcohol intake. Hence, the mechanism by which this mutation confers protection against alcoholism is unknown. To study this protective effect, the wild-type rat cDNA encoding rADH-47Arg was mutated to encode rADH-47His, mimicking the human mutation. The mutated cDNA was incorporated into an adenoviral vector and administered to genetically selected alcohol-preferring rats. The V(max) of rADH-47His was 6-fold higher (P<0.001) than that of the wild-type rADH-47Arg. Animals transduced with rAdh-47His showed a 90% (P<0.01) increase in liver ADH activity and a 50% reduction (P<0.001) in voluntary ethanol intake. In animals transduced with rAdh-47His, administration of ethanol (1g/kg) produced a short-lived increase of arterial blood acetaldehyde concentration to levels that were 3.5- to 5-fold greater than those in animals transduced with the wild-type rAdh-47Arg vector or with a noncoding vector. This brief increase (burst) in arterial acetaldehyde concentration after ethanol ingestion may constitute the mechanism by which humans carrying the ADH1B*2 allele are protected against alcoholism.
Asunto(s)
Alcohol Deshidrogenasa/genética , Alcoholismo/enzimología , Alcoholismo/prevención & control , Acetaldehído/sangre , Adenoviridae/genética , Alcohol Deshidrogenasa/metabolismo , Alcoholismo/genética , Alelos , Sustitución de Aminoácidos , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Línea Celular , Cartilla de ADN/genética , Modelos Animales de Enfermedad , Etanol/administración & dosificación , Vectores Genéticos , Humanos , Cinética , Mutagénesis Sitio-Dirigida , Mutación Puntual , Polimorfismo Genético , Ratas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transducción Genética , TransfecciónRESUMEN
Introducción: La gamma glutamil transferasa es una enzima hepática que aumenta su actividad ante varias enfermedades y por inducción enzimática provocada por determinados fármacos y drogas. La ingestión de alcohol produce un aumento en la actividad de esta enzima y disminuye sus valores al cabo de seis u ocho semanas luego de la ingestión. Este efecto permite que la gamma glutamil transferasa sea utilizada como un marcador biológico para el alcoholismo, y permita supervisar el tratamiento de deshabituación en pacientes alcohólicos. Objetivo: Determinar la existencia de interferencias en nuestro análisis relacionadas con diferentes parámetros en Química Clínica. Métodos: Se tomó la muestra de suero de 30 pacientes alcohólicos en tratamiento de deshabituación ingresados en el Hospital Psiquiátrico Provincial de Villa Clara y se les realizó la determinación in vitro de la gamma glutamil transferasa en suero por método cinético, en espectrofotómetro y en el analizador automático de química clínica (Hitachi); además, se les realizaron en dicho analizador las determinaciones de bilirrubina, colesterol, glucemia, urea, triglicéridos, entre otros, como criterio de exclusión para la investigación. Se realizó un Análisis de Regresión Lineal empleando el módulo correspondiente en el paquete estadístico STATISTICA 5.5 para determinar las interferencias. Resultados: Analizando los parámetros estadísticos de la ecuación obtenida, se observó que el modelo explica satisfactoriamente el 96,7 por ciento de la varianza observada en la variable dependiente. Entre las variables que forman parte de dicho modelo, se destaca la aparición de las relacionadas con los niveles séricos de fosfatasa alcalina, urea y colesterol; los productores del juego de reactivos informan que este último interfiere en la exactitud del resultado(AU)
Introduction: The gamma glutamyl transferase is a hepatic enzyme that increases its activity due to the presence of several illnesses and due to the enzymatic induction caused by some drugs, Alcohol ingestion produces an increase in the activity of this enzyme and reduces its value six or eight weeks after ingestion. This effect allows us to use gamma glutamyl transferase as a biological marker for alcoholism and to supervise the disaccustoming treatment in alcoholic patients. Objective: To determine the existence of interferences in our analysis concerning the different parameters in Clinical Chemistry. Methods: Samples from the serum of 30 hospitalized alcoholic patients that were receiving a disaccustoming treatment at the Provincial Psychiatric Hospital in Villa Clara were taken. These samples were submitted to an in vitro determination of the serum gamma glutamyl transferase using a kinetic method in a spectrophotometer and in an automatic analyzer of clinical chemistry (Hitachi). Additionally, the determinations of bilirubin, cholesterol, glycemia, urea, triglycerides, among others, were carried out in the above mentioned analyzer as an exclusion criterion for the research. A Lineal Regression Analysis using the corresponding module in the statistical package STATISTICA 5.5 was carried out with the aim of determining the interferences. Results: Analyzing the statistical parameters of the obtained equation, it was noticed that the model explains satisfactorily the 96,7percent of the variance observed in the dependent variable. Among the variables forming part of such a model it was noticed the appearance of those related to serumal levels of alkaline phosphatase, urea and cholesterol. The manufacturers of the set of reactives inform that cholesterol interferes with the accuracy of the result(AU)
Asunto(s)
Humanos , gamma-Glutamiltransferasa/sangre , Alcoholismo/enzimologíaRESUMEN
The population of Trinidad and Tobago is composed mainly of people of East Indian (Indo-Trinidadians) and African (Afro-Trinidadians) ancestry. Differences in alcoholism rates exist between these two ethnic groups, and researchers have investigated whether these differences can be explained in part by variations in the genes encoding the alcohol-metabolizing enzymes alcohol dehydrogenase (ADH) 1B and 1C, and aldehyde dehydrogenase (ALDH) 1 and 2. Studies have demonstrated that a certain variant of the gene encoding ADH1B (ADH1B*3) is associated with a reduced risk of alcoholism in Afro-Trinidadians, as is a variant of the gene encoding ADH1C (i.e., ADH1C*1) in Indo-Trinidadians. An ALDH2 variant shown to have protective effects primarily in East Asians was not found in either Trinidadian ethnic group. However, a variant in the gene encoding cytosolic ALDH1A (i.e. ALDH1A1*1/*2) was found to be associated with an increase in alcohol dependence in Indo-Trinidadians.
Asunto(s)
Alcohol Deshidrogenasa/genética , Alcoholismo/etnología , Aldehído Deshidrogenasa/genética , Pueblo Asiatico/genética , Población Negra/genética , Etanol/metabolismo , Alcohol Deshidrogenasa/metabolismo , Alcoholismo/enzimología , Alcoholismo/genética , Aldehído Deshidrogenasa/metabolismo , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Variación Genética , Humanos , Trinidad y Tobago/epidemiologíaRESUMEN
Among the different possible genes involved in the alcoholism etiology, the X-linked monoamine oxidase A gene is a good candidate. The aim of this study was to assess whether a functional VNTR polymorphism in the promoter region of the monoamine oxidase A gene is associated with alcoholism, comparing patients of both sexes. Ninety-three alcohol-dependent patients (51 males, 42 females) and 93 sex-matched normal controls were engaged. In the total sample, the genotype containing at least one three-repeat allele was significantly more frequent among alcohol-dependent patients than controls (P=0.01). However, when the two sexes were analyzed separately, the difference was statistically significant only for females. This is of particular interest as rates of alcoholism in Brazil are markedly lower in females. Our results suggest that this monoamine oxidase A polymorphism could play a role in susceptibility to alcoholism, which may differ across sexes.
Asunto(s)
Alcoholismo/genética , Monoaminooxidasa/genética , Polimorfismo Genético , Mujeres , Alcoholismo/enzimología , Alcoholismo/epidemiología , Brasil/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Repeticiones de Minisatélite/genética , Valores de Referencia , Caracteres SexualesRESUMEN
Excessive alcohol consumption may cause the development of pathologies in the liver and pancreas and various digestive tract cancers. The enzymes GSTM1, GSTT1, GSTP1, CYP1A1 and CYP2E1 are involved in the bioactivation and detoxification of a variety of xenobiotics present in food, organic solvents, tobacco smoke, drugs, pesticides, environmental pollutants and alcoholic drinks. Polymorphisms in the genes coding for these enzymes have been associated with susceptibility to different diseases, including ethanol-related diseases. To investigate whether these polymorphisms represent risk-modifying factors for ethanol-related diseases, a study was conducted involving 120 Brazilian alcoholics and 221 controls with similar ethnic backgrounds. The distribution of alcoholics groups was as follows: 65 with liver cirrhosis, 14 with chronic pancreatitis and 41 without cirrhosis or pancreatitis. The data revealed that carriers of the rare GSTP1 Val allele were at higher risk of liver cirrhosis and pancreatitis, since we found higher frequencies of the Val/Val genotype in alcoholics with liver cirrhosis (15.4%) and pancreatitis (28.6%) in comparison with alcoholics without disease (7.3%). No differences were found in the prevalences of the GSTM1 and GSTT1 null genotypes between alcoholics and the controls and no association was found between the rare CYP2E1 c2 allele and liver cirrhosis and pancreatitis. However, when the mutant CYP1A1 allele was compared between alcoholics and controls, the m2/m2 genotype was more prevalent in the liver cirrhosis alcoholics (7.7%) than in the controls (1.4%) and this difference was statistically significant (P = 0.03, OR = 5.33). In conclusion, our data indicate an association between occurrence of the Val/Val GSTP1 genotype and chronic pancreatitis and an association between the m2/m2 CYP1A1 genotype and alcoholic liver cirrhosis. This could indicate that persons with these genotypes are genetically more prone to the development of alcoholic pancreatitis and alcoholic cirrhosis, respectively.
Asunto(s)
Alcoholismo/enzimología , Alcoholismo/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Glutatión Transferasa/genética , Polimorfismo Genético , Aciltransferasas/genética , Adulto , Anciano , Alcoholismo/complicaciones , Secuencia de Bases , Estudios de Casos y Controles , Enfermedad Crónica , Cartilla de ADN/genética , Femenino , Frecuencia de los Genes , Humanos , Cirrosis Hepática Alcohólica/enzimología , Cirrosis Hepática Alcohólica/etiología , Cirrosis Hepática Alcohólica/genética , Masculino , Persona de Mediana Edad , Pancreatitis Alcohólica/enzimología , Pancreatitis Alcohólica/etiología , Pancreatitis Alcohólica/genéticaRESUMEN
We studied the distribution of GSTM1 phenotypes in 611 individuals from an ethnically mixed sample of the Brazilian population who died from various causes. No influence of age, gender, or ethnicity was detected on the phenotypic distribution. In a sub-sample of 66 alcoholic individuals compared with 399 non-alcoholics there was almost a doubling of the odds ratio for GSTM1(0) individuals in the alcoholic category. The incidence of hepatopathies was higher in this group as well, and we observed a significant association of the null phenotype with cirrhosis. An excess of null phenotypes (374/611) was observed, and the allelic distribution was: GSTM1*A = 0.168, *B = 0.089, and *0 (null) = 0.743.
Asunto(s)
Glutatión Transferasa/genética , Hepatopatías/enzimología , Hígado/enzimología , Alcoholismo/enzimología , Alcoholismo/etnología , Alcoholismo/genética , Brasil , Femenino , Regulación Enzimológica de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Glutatión Transferasa/metabolismo , Humanos , Hígado/metabolismo , Hepatopatías/etnología , Hepatopatías/genética , Masculino , Oportunidad Relativa , FenotipoRESUMEN
PURPOSE: To review the medical literature regarding the histopathologic and biochemical liver test abnormalities in chronic asymptomatic or oligosymptomatic alcoholics. METHODS: Review of articles in the MEDLINE and LILACS databases regarding serum levels and prevalence of alterations in aspartate-aminotransferase, alanine-aminotransferase, alkaline phosphatase, and total bilirubin, in relation to liver histopathology, with or without discrimination of types of histopathologic alteration. RESULTS: Global mean prevalence rates of aspartate-aminotransferase and alanine-aminotransferase alterations were 86.3% and 51.1%; in cases with steatosis they were 79.1% and 38.5%; and in cases of hepatitis, 90.1% and 58%. In all studies, prevalence rates of aspartate-aminotransferase alterations were significantly higher with lower variability than those of alanine-aminotransferase. Mean aspartate-aminotransferase levels were higher than 2N (N is the upper normal limit of the method employed) in all cases with hepatitis histopathology, while those of alanine-aminotransferase were 1.48N, in the same cases. Prevalence of alkaline phosphatase and total bilirubin abnormalities were 74.5% and 74.9% globally; in cases of steatosis, they were 70.9% and 67.9%; and in cases of hepatitis, 75.9% and 77.7%. Mean alkaline phosphatase levels were above the upper normal limit in all cases, but those of total bilirubin were above normal in 4 of 7 hepatitis studies. CONCLUSIONS: Prevalence of aspartate-aminotransferase alteration was consistently related to presence of histopathologic abnormalities; an enzyme level higher than 2N suggests the diagnosis of alcoholic hepatitis.
Asunto(s)
Alcoholismo/enzimología , Hígado/enzimología , Fosfatasa Alcalina/metabolismo , Bilirrubina/metabolismo , Enfermedad Crónica , Femenino , Humanos , Hígado/fisiopatología , Pruebas de Función Hepática , MasculinoRESUMEN
BACKGROUND: The purpose of this study was to compare the sensitivity and specificity of some new and traditional biological markers and indicators of health among Brazilian nondrinkers, drinkers, and alcohol-dependent patients. MATERIAL AND METHODS: We evaluated 130 nondrinkers, 167 drinkers, and 183 alcohol-dependent drinkers from Brazil who participated in the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence. A standardized WHO/ISBRA Interview Schedule provided background information on the subjects' characteristics including reported health problems and alcohol consumption. Blood samples were analyzed for aspartate aminotransferase (AST), carbohydrate deficient transferrin (CDT), gamma-glutamyltransferase (GGT), blood alcohol levels (BAL), and platelet adenylate cyclase activity (basal levels [AC] and levels after stimulation with Gpp(NH)p, cesium fluoride, and forskolin). RESULTS: The alcohol-dependent drinkers presented higher levels of AST, GGT, AC, CDT, and BAL than the nondrinkers and drinkers, whose levels were similar. Sex differences in the sensitivity of CDT and AC were found. The alcohol-dependent women presented a lower prevalence of abnormal values of CDT and Gpp(NH)p-stimulated AC than the alcohol-dependent men, despite the fact that they presented similar alcohol consumption levels. The alcohol-dependent drinkers presented a higher prevalence of clinical disorders than the nondrinkers and drinkers. The drinkers and alcohol-dependent patients presented significantly higher rates of gastritis than the nondrinkers. CONCLUSIONS: Sex differences in the sensitivity of CDT and AC suggest that these markers are not as sensitive at detecting excessive alcohol use in women as they are in men. If data from this Brazilian sample are compared with those reported for international samples, relevant differences are detected, which suggests that genetic and cultural differences should be considered in the selection of biological markers of heavy alcohol consumption.
Asunto(s)
Consumo de Bebidas Alcohólicas/sangre , Alcoholismo/sangre , Templanza , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/enzimología , Alcoholismo/epidemiología , Análisis de Varianza , Biomarcadores/sangre , Brasil/epidemiología , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes/estadística & datos numéricos , Factores Sexuales , Templanza/estadística & datos numéricosRESUMEN
BACKGROUND: Acute intermittent porphyria is a hereditary error of porphyrin metabolism in which the main metabolic defect is caused by a decrease in porphobilinogen deaminase activity. Previous work has demonstrated a higher prevalence of acute intermittent porphyria in the psychiatric patient population than in the general population. The goal of this study was evaluate 300 psychiatric patients and 150 control subjects to detect acute intermittent porphyria by measurement of porphobilinogen (PBG) deaminase activity in blood. METHODS: Screening for porphobilinogen deaminase activity was carried out by fluorometric measurement of porphyrins synthesized during 1 h in blood and the measurement of delta-aminolevulinic acid and porphobilinogen in urine. RESULTS: We found two psychiatric patients, one male and one female, with decreased porphobilinogen deaminase activity. When the families of these patients were studied, one brother was found to have an abnormality. Among controls, a woman was found to have the abnormality and her father was found to have typical features of the disease. CONCLUSIONS: These results indicate a prevalence of porphyria in Mexican psychiatric patients similar to controls, and that measurement of PBG deaminase activity is a good tool for defining acute intermittent porphyria carriers.
Asunto(s)
Depresión/complicaciones , Trastornos de la Personalidad/complicaciones , Porfiria Intermitente Aguda/epidemiología , Esquizofrenia Paranoide/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Anciano , Alcoholismo/sangre , Alcoholismo/complicaciones , Alcoholismo/enzimología , Trastorno de Personalidad Limítrofe/sangre , Trastorno de Personalidad Limítrofe/complicaciones , Trastorno de Personalidad Limítrofe/enzimología , Depresión/sangre , Depresión/enzimología , Femenino , Humanos , Hidroximetilbilano Sintasa/sangre , Masculino , México/epidemiología , Persona de Mediana Edad , Linaje , Trastornos de la Personalidad/sangre , Trastornos de la Personalidad/enzimología , Porfiria Intermitente Aguda/sangre , Porfiria Intermitente Aguda/complicaciones , Porfiria Intermitente Aguda/enzimología , Prevalencia , Esquizofrenia Paranoide/sangre , Esquizofrenia Paranoide/enzimología , Intento de SuicidioRESUMEN
BACKGROUND: The goal of this study was to find the association between low arylsulfatase A (ASA) activity and psychiatric disorders in chronic alcoholic patients. METHODS: The study was carried out in 30 chronic alcoholic patients (27 male, 3 female); age range was 25-65 years. There were 20 normal controls (18 males, 2 females), and age range was 24-67 years. ASA and routine aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity laboratory tests were measured in blood serum from all patients and control subjects. RESULTS: Alcoholic patients with psychiatric disorders have ASA average values of 68.25 nmol/mL/4 h. This is less than averages found in the alcoholics without psychiatric disorders group (82.48 nmol/mL/4 h) and the control group (90.8 nmol/mL/4 h). There were no statistically significant differences among the three groups studied. Alcoholic subjects with elevated activity of AST and ALT (n = 10) have ASA activity average values of 134.82 nmol/mL/4 h), which is 48.8% higher than the control group (90.6 nmol/mL/4 h). These means show statistically significant differences (p <0.05). CONCLUSIONS: Results indicate an association between low serum ASA activity and alcoholism. The appearance of psychiatric manifestations could be related to the low activity of this enzyme in chronic alcoholic patients. Alcoholic patients with elevated enzyme activity of AST and ALT in sera also have elevated sera arylsulfatase A (ASA) activity. We consider that these findings may be useful for evaluating the psychiatric state as a prognosis in chronic alcoholic patients, and should be a routine laboratory test in alcoholic patients.