Genetic Polymorphisms in the 5′-Flanking Region Change Transcriptional Regulation of the Human Cytochrome P450IIE1 Gene1

Hayashi, Shin Ichi; Watanabe, Junko; Kawajiri, Kaname

doi:10.1093/oxfordjournals.jbchem.a123619

Cited by 586 publications

(419 citation statements)

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“…[15][16][17] Briefly, the genomic DNA samples were obtained from the white blood cells with a DNA Extractor WB Kit (Wako, Japan), and then amplified by PCR (Perkin-Elmer 2400, USA) for each of ALDH2, ADH2 and CYP2E1 loci. The PCR products were digested into the DNA fragments by specific restrictive endonuclease for the enzymes, ie., MobII (Wako, Japan) for ALDH2, MaeIII (Boehringer, Germany) for ADH2, and Rsa1 and Pst1 (Wako, Japan) for CYP2E1.…”

Section: Methodsmentioning

confidence: 99%

Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers

et al. 2002

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Orientals have unique genetic polymorphisms in ethanol metabolizing enzymes, such as alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2) and cytochrome P450-2E1 (CYP2E1). Of the three studies conducted to clarify the influence of ALDH2 genotypes on sensitivity to the pressor effects of alcohol in Japanese, only one was suggested, though indirectly, higher sensitivity in drinkers having the genotype of inactive ALDH2. This discrepancy prompted us to determine ADH2, ALDH2 and CYP2E1 genotypes in the genomic DNA extracted from white blood cells of 855 healthy middle-aged Japanese men, and to analyse the associations with the alcohol-blood pressure (BP) relationship. No marked differences were found in the relationship among the genotypes of ALDH2, although the subjects with intact ALDH2 showed a slightly higher

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Section: Methodsmentioning

confidence: 99%

Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers

et al. 2002

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“…Several studies were conducted on this gene with regard to the presence of Restriction Fragment Length Polymorphisms (RFLP) for the enzymes RsaI and PstI in the CYP2E1 5′ flanking region (Watanabe et al, 1990), as well as the effects of these polymorphisms in the transcriptional activity of the gene (Hayashi et al, 1991).…”

Section: Multiple Correlation Between Ethanol or Zcyd-inducted Cyp2e1mentioning

confidence: 99%

Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme

Naselli

Catanzaro

Bellavia

et al. 2014

Gene

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach, we studied the polymorphisms and methylation of sites contained in the 5′ flanking region of the metabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associated with the increase of enzyme expression. Interestingly, the Rsa/Pst haplotype differentially influenced CYP2E1 enzyme expression. In addition, regarding the Variable Number of Tandem Repeats polymorphism, cells with A4/A4 genotype showed a greater expression inhibition (ranging from 20% to 30%) compared with others carrying the A2/A2 one, while those cells bringing A2/A3 genotype showed an increase of expression (of 25%, about). Finally, we demonstrated for the first time that the A2 and A3 CYP2E1 alleles play a more important role in the expression of the enzyme, compared with other (epi)genetic factors, since they are binding sites for trans-acting proteins.

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“…Se cree que la coordinación de la expresión de estas dos familias enzimáticas es necesaria para garantizar la eficiencia en la desintoxicación de mutágenos como los hidrocarburos aromáticos policíclicos, las nitrosaminas, los fenoles, el cloroformo, el nitrocloroetileno, el benceno, el tolueno y otros disolventes orgánicos. Por lo tanto, con su determinación estas enzimas se convierten en biomarcadores de susceptibilidad (41)(42)(43)(44)(45).…”

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Evaluación del daño en el ADN y vigilancia biológica de la exposición laboral a solventes orgánicos, 2006

et al. 2008

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Introducción. La exposición a solventes es uno de los mayores riesgos potenciales para millones de trabajadores en el mundo; los solventes generan contaminación ambiental y desencadenan problemas de salud pública. Objetivo. Determinar los niveles de los metabolitos benceno, tolueno y xileno, los polimorfismos de las enzimas CYP2E1, GSTM1, GSTT1 y el daño del ADN mediante el ensayo del cometa. Materiales y métodos. Se llevó a cabo un estudio descriptivo de corte transversal para la determinación de polimorfismos genéticos y prueba del cometa en 90 trabajadores pertenecientes a cinco empresas. Se aplicó una encuesta, se tomaron muestras de sangre y de orina, se midieron las concentraciones de fenol, ácido hipúrico orto y meta-metilhipúrico. Se hizo el análisis estadístico y se exploraron posibles asociaciones. Resultados. El 34,4% eran trabajadores con exposición directa a solventes. En este grupo se evidenciaron concentraciones superiores a los límites permisibles en 3,3% para fenol, en 6,6% para ácido hipúrico, en 3,3% para ácido orto-metilhipúrico y en 36,7% para ácido metametilhipúrico, mayor longitud promedio de la cola del cometa (19,5 µm) y un incremento del porcentaje de células con daño medio (19,0%) (p=0,0007). El porcentaje de individuos expuestos con genotipos ausentes para las enzimas GSTT1 y GSTM1 fue de 46,7% y de 56,8%, respectivamente. Conclusión. El uso de biomarcadores de exposición, efecto y susceptibilidad, se ha convertido en una herramienta fundamental para la evaluación del riesgo asociado con la exposición a agentes tóxicos.Palabras clave: daño del ADN/genética, exposición profesional, solventes/toxicidad, salud pública DNA damage assessment and biological monitoring of occupational exposure to organic solvents, 2006Introduction. Exposure to solvents is one of the highest potential risks for millions of workers in the world; they can generate substantial environmental pollution leading to outbreaks of public health problems. Objective. Blood levels were determined for metabolites of benzene, toluene and xylene, and polymorphisms for enzymes CYP2E1, GSTM1, GSTT1 were characterized. Damage to DNA was assessed by the comet assay for exposure to organic solvents. Materials and methods. A cross-sectional study was undertaken in 90 employees from 5 different companies. A survey form was administered; blood was sampled to detect the genetic polymorphisms and to apply the comet assay (single cell gel electrophoresis) to detect DNA fragmentation. The concentrations of phenol, ortho and meta methylhippuric acids were measured in urine. Statistical analyses explored the possible associations. Results. The percentage of workers directly exposed to solvents was 34.4%. In this group, the evidence indicated concentrations higher than the permitted limits: 3.3% for phenol, 6.6% for

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Genetic Polymorphisms in the 5′-Flanking Region Change Transcriptional Regulation of the Human Cytochrome P450IIE1 Gene1

Cited by 586 publications

References 40 publications

Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers

Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers

Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme

Evaluación del daño en el ADN y vigilancia biológica de la exposición laboral a solventes orgánicos, 2006

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