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  • Title: An investigation of whether polymorphisms of cytochrome P4502E1 are genetic markers of susceptibility to alcoholic end-stage organ damage in a Chinese population.
    Author: Chao YC, Young TH, Chang WK, Tang HS, Hsu CT.
    Journal: Hepatology; 1995 Nov; 22(5):1409-14. PubMed ID: 7590656.
    Abstract:
    The human cytochrome P4502E1 gene (P4502E1), coding for an ethanol-inducible nitrosamine-metabolizing P-450, is involved in the metabolism of ethanol and many known carcinogens. Recently, restriction fragment length polymorphisms (RFLPs) within the P4502E1 have been suggested as genetic markers of susceptibility to alcohol-induced liver disease but the previous studies disagree whether alcoholics with c1 or c2 allele are more susceptible to alcohol-induced liver diseases. Using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the RsaI and PstI polymorphism of P4502E1 in 77 Chinese alcoholic patients (54 with alcohol-induced cirrhosis and 23 with acute alcohol-induced pancreatitis) and 164 non-alcoholics and compared them with previously published data. The PCR-RFLPs showed three P4502E1 genotypes: type A, homozygote c1/c1; type B, heterozygote c1/c2; and type C, homozygote c2/c2. The RsaI and PstI polymorphism of P4502E1 were completely linked in both Chinese alcoholics and nonalcoholic controls. The rare allele (c2) occurs at similar frequency of 0.232 and 0.234 (P > .05) in nonalcoholic controls and alcoholics, respectively. The genotype distributions of P4502E1 between Chinese alcoholics and nonalcoholics are not significantly different. The genotype and allele frequencies of P4502E1 for Chinese are significantly different from those of Swedes, European-Americans, and African-Americans, respectively (P < .00001), but very similar to Japanese (P > .05). In conclusion, ethnic variations exist between Asians and Caucasians and between Asians and African-Americans. No allelic variants at loci associated with RsaI/PstI RFLPs result in phenotypes displaying greater susceptibility to alcohol-induced cirrhosis or alcoholism in Chinese populations, which contradicts previous reports from Japanese groups.
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