RT Journal Article
SR Electronic
T1 CYP3A5 GENETIC POLYMORPHISMS IN DIFFERENT ETHNIC POPULATIONS
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 884
OP 887
DO 10.1124/dmd.105.003822
VO 33
IS 7
A1 Roy, Jean-Nicholas
A1 Lajoie, Julie
A1 Zijenah, Lynn S.
A1 Barama, Azemi
A1 Poirier, Charles
A1 Ward, Brian J.
A1 Roger, Michel
YR 2005
UL http://dmd.aspetjournals.org/content/33/7/884.abstract
AB Cyp3A5 activity varies within any given ethnic population, suggesting that genetic variation within the Cyp3A5 gene may be the most important contributor to interindividual and interracial differences in Cyp3A-dependent drug clearance and response. The full extent of Cyp3A5 polymorphism in a white and an indigenous African population was analyzed using DNA direct sequencing procedures. The presence of 10 and 12 single nucleotide polymorphisms was detected in the white and African samples, respectively. Thirteen novel mutations occurring at low frequencies were identified in these populations. Significant differences were observed in the distribution of Cyp3A5*3, Cyp3A5*6, and Cyp3A5*7 alleles among white and African populations. The frequency of Cyp3A5*3 allele in white Canadians (∼93%) is higher than in Zimbabweans (77.6%) (p < 0.001). In contrast, Cyp3A5*6 and Cyp3A5*7 alleles are relatively frequent in African subjects (10–22%) but absent in white subjects (p < 0.001). These differences may reflect evolutionary pressures generated by environmental factors in geographically distinct regions. However, the genetic polymorphism of Cyp3A5 alone does not explain the interindividual differences in Cyp3A-mediated metabolism. The American Society for Pharmacology and Experimental Therapeutics