Comparison of polymorphic CYP2D6, CYP2C19 and CYP2A6 in Canadian Native Indian, Caucasian and Chinese populations

• Main Author: Nowak, Maciej P.
• Format: Thesis
• Language: English
• Published: 1997
• Subjects: Bering Strait; Indian
• Online Access: http://hdl.handle.net/1807/11815; http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29327.pdf

grantor: University of Toronto A number of human cytochrome P450 enzymes are polymorphically expressed. This results in inter-individual differences in the ability to metabolize substrate drugs. More importantly, they exhibit significant inter-ethnic differences in the frequencies of mutant alleles and frequencies of the poor metabolizer genotype and phenotype. Although P450 enzymes have been studied extensively in Caucasian and Asian populations, very little is known about their genetic variation in Canadian Native Indians. Mitochondrial DNA studies have shown that Canadian Native Indians are descendants of north Asian populations which crossed the Bering Strait between 13,000 and 30,000 years ago. This agrees with previous evidence gathered from linguistic, dental and morphological studies. We have therefore hypothesized that Canadian Native Indians will resemble Asians, and differ from Caucasians, with respect to the frequencies of CYP2D6, CYP2C19 and CYP2A6 mutant alleles. We have studied the screened 159 Canadian Native Indian subjects for CYP2C19 (CYP2C19*2 and CYP2C19*3) and CYP2A6 (CYP2A6*2 and CYP2A6*3). These data have been analyzed and compared to Caucasian and Asian data previously reported in literature and data from our own laboratory. Canadian Native Indians were significantly different from both Caucasian and Asian populations with respect to the genotype patterns of both CYP2C19 and CYP2A6. This study was unique in that it investigated both the CYP2C19 and CYP2A6 polymorphisms in one population, thereby allowing us to determine whether there was any association between the CYP2C19 and CYP2A6 genotypes. Analysis of Canadian Native Indians suggests that there is an association between the presence of the CYP2C19 and CYP2A6 mutant alleles such that the co-occurrence of these two alleles is higher than would be predicted based on their frequencies in this population. (Abstract shortened by UMI.) M.Sc.