Nicotine metabolism and CYP2A6 allele frequencies in Koreans

CYP2A6 is a major catalyst of nicotine metabolism to cotinine, Previously, we demonstrated that the interindividual difference in nicotine metabolism is related to a genetic polymorphism of the CYP2A6 gene in Japanese. To cla rify the ethnic differences in nicotine metabolism and frequencies of CYP2A 6 alleles, we studied nicotine metabolism and the CYP2A6 genotype in 209 Ko reans. The cotinine/nicotine ratio of the plasma concentration 2 h after ch ewing one piece of nicotine gum was calculated as an index of nicotine meta bolism. The genotypes of CYP2A6 gene (CYP2A6*1A, CYP2A6*1B, CYP2A6*2, CYS2A 6*3, CYP2A6*4 and CYP2A6*5) were determined by polymerase chain reaction (P CR)-restriction fragment length polymorphism or allele specific(AS)-PCR. Th ere were ethnic differences in the allele frequencies of CYP2A6*1A, CYP2A6* 2B, CYP2A6*4 and CYP2A6*5 between Koreans (45.7%, 42.8%, 11.0% and 0.5%, re spectively) and Japanese (42.4%, 37.5%, 20.1% and 0%, respectively, our pre vious data). Similar to the Japanese, no CYP2A6*2 and CYP2A6*3 alleles were found in Koreans, The homozygotes of the CYP2A6*4 allele (four subjects) w ere completely deficient in cotinine formation, being consistent with the d ata among Japanese. The heterozygotes of CYP2A6*4 tended to possess a lower metabolic ratio (CYP2A6*1A/CYP2A6*4, 4.79 +/-3.17; CYP2A6*1B/CYP2A6*4, 7.4 3 +/- 4.97) than that in subjects without the allele (CYP2A6*1A/CYP2A6*1A, 7.42 +/- 6.56; CYP2A6*1A/CYP2A6*1B, 9.85 +/- 16.12; CYP2A6*1B/CYP2A6*1B, 11 .33 +/- 9.33). The subjects who possess the CYP2A6*1B allele appeared to sh ow higher capabilities of cotinine formation. It was confirmed that the int erindividual difference in nicotine metabolism was closely related to the g enetic polymorphism of CYP2A6, The probit plot of the metabolic ratios in K oreans (8.73 +/- 11.88) was shifted to a higher ratio than that in the Japa nese (3.78 +/- 3.09), In each genotype group, the Korean subjects revealed significantly higher metabolic ratios than the Japanese subjects, The ethni c difference in cotinine formation might be due to environmental and/or die t factors as well as genetic factors. Pharmacogenetics 11:317-323 (C) 2001 Lippincott Williams & Wilkins.