Cytochrome P4502C9 (CYP2C9) allele frequencies in canadian native indian and inuit populations

CYP2C9 is the major P450 2C enzyme in human liver and contributes to the me tabolism of a number of clinically important substrate drugs. This polymorp hically expressed enzyme has been studied in Caucasian, Asian, and to some extent in African American populations, but little is known about the genet ic variation in Native American populations. We therefore determined the 2C 9*2 (Arg(144)Cys) and 2C9*3 (Ile(359)Leu) allele frequencies in 153 Native Canadian Indian (CNI) and 151 Inuit subjects by PCR-RFLP techniques. We als o present genotyping data for two reference populations, 325 Caucasian (whi te North American) and 102 Chinese subjects. Genotyping analysis did not re veal 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, b ut was present in CNI and Caucasian subjects at frequencies of 0.03 and 0.0 8-0.15, 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 popul ation 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 poly morphisms exist in this Inuit group one would not anticipate any CYP2C9 poo r metabolizer subjects among this population.