title: CYP3A5 genetic polymorphisms in different ethnic populations.
abstract: 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 (approximately 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.
authors.affiliation: Laboratoire d'Immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Canada.
authors.forename: Jean-Nicholas
authors.initials: JN
authors.lastname: Roy
authors.forename: Julie
authors.initials: J
authors.lastname: Lajoie
authors.forename: Lynn S
authors.initials: LS
authors.lastname: Zijenah
authors.forename: Azemi
authors.initials: A
authors.lastname: Barama
authors.forename: Charles
authors.initials: C
authors.lastname: Poirier
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.forename: Michel
authors.initials: M
authors.lastname: Roger
mesh_terms: D001483:Base Sequence; D044383:Black People; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D011110:Polymorphism, Genetic; D044465:White People
chemical_list: D017931:DNA Primers; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A