Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations

The 4'-hydroxylation of S-mephenytoin is polymorphic in man. The poor metabolizer (PM) phenotype exhibits a lower frequency in Caucasians (2-5%) compared to Oriental populations (13-23%). Previous studies from our laboratory have described two mutations (CYP2C19(m1) and CYP2C19(m2)) which account for similar to 100% of Oriental and similar to 85% of Caucasian PM alleles. The present study examined whether the genotype predicted the phenotype in Japanese, Filipino and Saudi Arabian populations, and compared the frequencies of the defective CYP2C19 alleles in these populations with those found in European-Americans, Chinese-Taiwanese, and African-Americans from North Carolina. Among 53 Japanese, 15% were PMs and among 52 Filipinos 23% were PMs. Among 97 Saudi Arabians, only two were PMs. There was a complete concordance between genotype and phenotype in all three populations. The incidence of CYP2C19(m1) was 0.23 (95% confidence limits 0.15-0.31) in Japanese, 0.39 (95% confidence limits 0.29-0.48) in Filipinos, 0.32 (95% confidence limits 0.26-0.38) in Chinese-Taiwanese, 0.15 (95% confidence limits 0.10-0.20) in Saudi Arabians, 0.13 (95% confidence limits 0.08-0.17) in European-Americans, and 0.25 in African-Americans from North Carolina (95% confidence limits 0.14-0.31). The incidence of CYP2C19(m1) in Saudi Arabians was similar to that found in European-Americans, and significantly lower-than that found in Oriental populations for African-Americans (p < 0.05). CYP2C19(m2) was not found in European-Americans, Saudi Arabians or African-Americans (95%, confidence limits 0-0.014). The incidence of CYP2C19(m2) in the three Oriental populations ranged from 0.10 (95% confidence limits 0.05-0.17) in Japanese and 0.08 (95% confidence limits 0.03-0.13) in Filipinos to 0.06 (95% confidence limits 0.03-0.08) in Chinese-Taiwanese.