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Mutations in the Exons and Exon‐Intron Junction Regions of Human Cytochrome P‐4502E1 Gene and Alcoholism
Author(s) -
Itoga Sakae,
Nomura Fumio,
Harada Shoji,
Tsutsumi Mikihiro,
Takase Shujiro,
Nakai Toshiaki
Publication year - 1999
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1999.tb04526.x
Subject(s) - exon , intron , gene , genetics , biology , mutation , exon trapping , alternative splicing
Cytochrome P‐4502E1 (CYP2E1) is a major component of the microsomal ethanol‐oxidizing system (MEOS) and is also involved in the metabolism of a variety of foreign compounds, including carcinogens. It has been shown that there are interindividual variations in the expression of human CYP2E1. Gene‐environmental interactions have been suggested to account for the difference. In this study, we screened nine exons and exonintron junctions of the human CYP2E1 gene for detecting allelic variants in genomic DNA samples obtained from 115 Japanese controls, 96 alcoholics, and 44 patients with alcoholic liver diseases. A novel missense mutation in exon 2 (V72L) was found in Japanese controls, but the frequency was low (2.6%). In addition, two novel silent mutations (T303T and F420F), together with one mutation in intron 2, were found. However, no association of these mutations with alcoholism and alcoholic liver diseases was found. Our data indicate that nucleotide replacement in the open reading frame of CYP2E1 gene is not a major factor for interindividual differences in expression of CYP2E1 and susceptibility to alcohol‐related disorders.