GENETIC-POLYMORPHISM OF DEBRISOQUINE (CYP2D6) AND PROGUANIL (CYP2C19)IN SOUTH-PACIFIC POLYNESIAN POPULATIONS

Objective: Genetic oxidation polymorphisms of debrisoquine (CYP2D6) an d proguanil (CYP2C19) were studied in unrelated healthy South Pacific Polynesian volunteers recruited in the South Island of New Zealand. Me thods: Phenotyping for CYP2D6 and CYP2C19 activities was determined us ing debrisoquine and proguanil, respectively, as probe drugs by measur ing the urinary metabolic ratio of parent drug and its metabolite. Res ults: Of 100 Polynesian subjects phenotyped, the metabolic ratio of de brisoquine ranged from 0.01 to 9.94. Therefore, all South Pacific Poly nesians were classified as extensive metabolizers of debrisoquine acco rding to previously established criteria of the antimode. The prevalen ce of poor metabolizers of debrisoquine (CYP2D6) in this Polynesian po pulation is 0% (95% confidence interval of 0-3.6%). Oxidation polymorp hism of CYP2C19 using proguanil as a probe was also studied in 59 Poly nesian volunteers. The frequency distribution of the proguanil/cyclogu anil ratio was bimodal. The proguanil/cycloguanil ratios for these sub jects ranged from 0.09 to 34.4. Using a recommended proguanil/cyclogua nil ratio cut-off point of 10 established in Caucasian populations, ei ght Polynesian subjects were identified as poor metabolizers of progua nil (CYP2C19), which corresponds to a poor metabolizer phenotype frequ ency of 13.6% (a 95% confidence interval of 5.9-24.6%). Conclusion: Th e incidence of poor metabolizer phenotypes for debrisoquine (CYP2D6) i n South Pacific Polynesians appears to lower than in Caucasian populat ions, while the prevalence of poor metabolizers for proguanil (CYP2C19 ) in this ethnic population is higher. The frequencies of the poor met abolizer phenotype for debrisoquine and also for proguanil in South Pa cific Polynesians are similar to those reported in Asian populations.