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(m 2)) which account for similar to 100% of Oriental and similar to 85% o f Caucasian PM alleles. The present study examined whether the genotyp e predicted the phenotype in Japanese, Filipino and Saudi Arabian popu lations, 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 Japanes e, 15% were PMs and among 52 Filipinos 23% were PMs. Among 97 Saudi Ar abians, only two were PMs. There was a complete concordance between ge notype and phenotype in all three populations. The incidence of CYP2C1 9(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 limi ts 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 Euro pean-Americans, and 0.25 in African-Americans from North Carolina (95% confidence limits 0.14-0.31). The incidence of CYP2C19(m1) in Saudi A rabians was similar to that found in European-Americans, and significa ntly lower-than that found in Oriental populations for African-America ns (p < 0.05). CYP2C19(m2) was not found in European-Americans, Saudi Arabians or African-Americans (95%, confidence limits 0-0.014). The in cidence 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% confid ence limits 0.03-0.13) in Filipinos to 0.06 (95% confidence limits 0.0 3-0.08) in Chinese-Taiwanese.