title: Comparisons of CYP2A6 genotype and enzyme activity between Swedes and Koreans.
abstract: The aim was to compare cytochrome P450 2A6 (CYP2A6) genotype and enzyme activity between Swedes and Koreans, and to investigate the influence of genotype, sex, age, cigarette smoking and oral contraceptive (OC) use on enzyme activity. The study involved 190 Swedes and 144 Koreans. Genotyping for CYP2A6*1B, *1×2, *4, *5, *7, *8, *9, *10, *18 and *19 alleles was done. Using caffeine as a probe, in vivo CYP2A6 activity was estimated by the 17U/17X urinary ratio. Multiple regression analysis indicated ethnicity (p=0.0001) and CYP2A6 genotype (p=0.006), but not sex, age, cigarette smoking or OC use as predictors of CYP2A6 activity. There were significant differences in CYP2A6 genotype distribution and enzyme activity between Swedes and Koreans. Functional CYP2A6 alleles and rapid genotypes were more frequent in Swedes, whereas the defective alleles and slow genotypes were more frequent in Koreans (p≤0.0001). Distribution of log 17U/17X was bimodal in Koreans but unimodal in Swedes with a common antimode at 0.01, classifying 3.16% of Swedes and 18.75% of Koreans as slow metabolizers. CYP2A6 activity was higher in Swedes compared to Koreans (p<0.0001), even among carriers of rapid genotypes. We report major differences in CYP2A6 enzyme activity between Swedes and Koreans mainly due to CYP2A6 genetic variation but not exclusively.
authors: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors: Natasa
authors: N
authors: Djordjevic
authors: Juan Antonio
authors: JA
authors: Carrillo
authors: Marieke P J
authors: MP
authors: van den Broek
authors: Junko
authors: J
authors: Kishikawa
authors: Hyung-Keun
authors: HK
authors: Roh
authors: Leif
authors: L
authors: Bertilsson
authors: Eleni
authors: E
authors: Aklillu
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D044466:Asian People / Q000235:genetics*; D002110:Caffeine / Q000652:urine; D003276:Contraceptives, Oral / Q000494:pharmacology; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D005838:Genotype; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D012907:Smoking / Q000378:metabolism; D013548:Sweden; D044465:White People / Q000235:genetics*
chemical_list: D003276:Contraceptives, Oral; D002110:Caffeine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6