Alcohol and alcoholism (Oxford, Oxfordshire) · 2009
A promoter polymorphism in the ALDH2 gene affects its basal and acetaldehyde/ethanol-induced gene expression in human peripheral blood leukocytes and HepG2 cells.
Сравнительное исследованиеСтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kimura Yukiko, Nishimura Fusae T, Abe Shuntaro, Fukunaga Tatsushige, Tanii Hideji, Saijoh Kiyofumi
Аннотация
AIMS: To assess the effect of the -360G/A polymorphism in the promoter region of the human aldehyde dehydrogenase-2 (ALDH2) gene on its transcription, basal and acetaldehyde/ethanol-induced gene expression was examined by in vivo and in vitro experiments.
METHODS: Human peripheral blood leukocytes were collected before and after alcohol ingestion (0.4 g/kg body weight) in 21 healthy young Japanese volunteers with a deficient phenotype of ALDH2 ((487)Glu/Lys), and the levels of ALDH2 mRNA were quantified by real-time RT-PCR. The transcriptional activity of the ALDH2 promoter was investigated by a reporter assay using HepG2 cells in the presence or absence of acetaldehyde/ethanol.
RESULTS: The basal level of ALDH2 mRNA was significantly higher in -360A heterozygous subjects than in -360G homozygous subjects. In all subjects, regardless of the genotype, ALDH2 mRNA increased following ethanol ingestion. The promoter activity of a reporter plasmid for -360G was significantly lower than that of a reporter plasmid for -360A. Exposure to acetaldehyde induced a significant increase in the transcriptional activity of the -360G reporter, but not the -360A reporter.
CONCLUSIONS: In vivo and in vitro experiments showed that the -360G allele has lower basal transcriptional activity than the -360A allele, whereas acetaldehyde/ethanol-induced gene expression, in general, seems to be more enhanced in individuals homozygous for the -360G allele than in those with the -360A allele. Thus, the promoter polymorphism may be involved in individual differences in acetaldehyde elimination.
METHODS: Human peripheral blood leukocytes were collected before and after alcohol ingestion (0.4 g/kg body weight) in 21 healthy young Japanese volunteers with a deficient phenotype of ALDH2 ((487)Glu/Lys), and the levels of ALDH2 mRNA were quantified by real-time RT-PCR. The transcriptional activity of the ALDH2 promoter was investigated by a reporter assay using HepG2 cells in the presence or absence of acetaldehyde/ethanol.
RESULTS: The basal level of ALDH2 mRNA was significantly higher in -360A heterozygous subjects than in -360G homozygous subjects. In all subjects, regardless of the genotype, ALDH2 mRNA increased following ethanol ingestion. The promoter activity of a reporter plasmid for -360G was significantly lower than that of a reporter plasmid for -360A. Exposure to acetaldehyde induced a significant increase in the transcriptional activity of the -360G reporter, but not the -360A reporter.
CONCLUSIONS: In vivo and in vitro experiments showed that the -360G allele has lower basal transcriptional activity than the -360A allele, whereas acetaldehyde/ethanol-induced gene expression, in general, seems to be more enhanced in individuals homozygous for the -360G allele than in those with the -360A allele. Thus, the promoter polymorphism may be involved in individual differences in acetaldehyde elimination.