An investigation of whether polymorphisms of cytochrome P4502E1 are genetic markers of susceptibility to alcoholic end-stage organ damage in a chinese population
✍ Scribed by You-Chen Chao; Tong-Ho Young; Wei-Kuo Chang; Hung-Shang Tang; Chung-Te Hsu
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 621 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
The human cytochrome P4502El 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 c l or c2 allele are more susceptible to alcohol-induced liver disease. Using a polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) 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 nonalcoholics and compared them with previously published data. The PCRRFLPs showed three P4502E1 genotypes: type A, homozygote cl/cl; type B, heterozygote cl/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 sig nificantly different. The genotype and allele frequencies of P4502E1 for Chinese are significantly different from those of Swedes, European-Americans, and African-Americans, respectively (P < .OOOOl), 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 RsaUPstI RFLPs result in phenotypes displaying Abbreviations: ADH, alcohol dehydrogenase; MEOS, microsomal ethanol oxidizing system; mRNA, messenger RNA; RFLP, restriction fragment length polymorphism; HBsAg, hepatitis B surface antigen; HBc, hepatitis B core; PCR, polymerase chain reaction.