Genetic polymorphism of CYP2E1, ADH2, and ALDH2 in Mexican-Americans.
The major enzymes involved in the metabolism of ethanol are alcohol dehydrogenases (ADH) and aldehyde dehydrogenase (ALDH). Some of the isozymes of ADH are expressed polymorphically. Studies investigating a causal link between ADH expression and alcoholic liver disease (ALD) have so far produced conflicting results. The cytochrome P450 2E1 (CYP2E1) represents a second enzyme that can metabolize ethanol. Although normally a minor route of metabolism, its role in chronic alcoholics may be proportionately greater than in nonalcoholics because CYP2E1 is inducible by ethanol. An Rsa I restriction fragment length polymorphism (RFLP) in the 5'-flanking region of the CYP2E1 gene has been identified. Studies have shown that the mutant allele demonstrates greater transcriptional rate, protein level, and enzyme activity when compared with the wild-type allele. The association between the Rsa I site polymorphism and ALD has been reported. In this report, we examined the genotypes of ADH2(2), ALDH2(2), and CYP2E1 in a group of healthy subjects of Mexican-American descent. The ADH2(2) and ALDH2(2) frequencies are 6% and 0%, respectively, which are similar to those which have been reported for Caucasians. In contrast, the Rsa I allele frequency of the CYP2E1 gene is 16%, which is significantly higher than in Caucasians. The high RsaI allele frequency found in Mexican-Americans suggests that it might play a role in the development of ALD in this rapidly growing minority population where ALD is common.
Wan
Y J
YJ
Department of Pathology, Harbor-UCLA Medical Center, Torrance 90509, USA.
Poland
R E
RE
Lin
K M
KM
D000426:Alcohol Dehydrogenase / Q000096:biosynthesis / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D044465:White People / Q000235:genetics
D007527:Isoenzymes; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase