title: Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations.
abstract: CYP2C9 is the major P450 2C enzyme in human liver and contributes to the metabolism of a number of clinically important substrate drugs. This polymorphically expressed enzyme has been studied in Caucasian, Asian, and to some extent in African American populations, but little is known about the genetic variation in Native American populations. We therefore determined the 2C9*2 (Arg144Cys) and 2C9*3 (Ile359Leu) allele frequencies in 153 Native Canadian Indian (CNI) and 151 Inuit subjects by PCR-RFLP techniques. We also present genotyping data for two reference populations, 325 Caucasian (white North American) and 102 Chinese subjects. Genotyping analysis did not reveal any 2C9*4 alleles in the CNI, Inuit, Caucasian, or Chinese individuals. The 2C9*2 allele appears to be absent in Chinese and Inuit populations, but was present in CNI and Caucasian subjects at frequencies of 0.03 and 0.08-0.15, respectively. The 2C9*3 allele was not detected in the Inuit group, but occured in the CNI group (f = 0.06) at a frequency comparable to that of other ethnic groups. This group of Inuit individuals are the first population in which no 2C9*2 or *3 alleles have been detected so far. Therefore, these alleles may be extremely rare or absent, and unless other novel polymorphisms exist in this Inuit group one would not anticipate any CYP2C9 poor metabolizer subjects among this population.
authors.affiliation: Division of Pediatric Clinical Pharmacology and Toxicology, the Children's Mercy Hospital and Clinics, Kansas City, MO 64108, USA. agaedigk@cmh.edu
authors.forename: A
authors.initials: A
authors.lastname: Gaedigk
authors.forename: W L
authors.initials: WL
authors.lastname: Casley
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: E M
authors.initials: EM
authors.lastname: Sellers
authors.forename: M
authors.initials: M
authors.lastname: Jurima-Romet
authors.forename: J S
authors.initials: JS
authors.lastname: Leeder
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D001213:Asian; D002170:Canada; D002681:China / Q000208:ethnology; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D004930:Inuit / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase