GENETIC POLYMORPHISMS OF CYP2D6, CYP1A1 AND CYP2E1 IN THE SOUTH-AMERINDIAN POPULATION OF CHILE

Polymorphisms of cytochrome P450 genes show pronounced interethnic var iation and have not been previously studied in the South-Amerindian po pulation, which probably has an Asian origin. Therefore, a similar dis tribution of allelic and haplotype frequencies of cytochrome P450 gene s to Asian populations might be expected in South-Amerindians. We anal ysed the allelic frequencies and haplotype distribution for CYP2D6, CY P1A1 and CYP2E1 genes in the South-Amerindian population of Chile (Map uche, n = 84) by Southern blot or polymerase chain reaction-restrictio n fragment length polymorphism. Similar allelic frequencies and haplot ype distribution for the CYP2E1 gene between Mapuches and Asian popula tions were observed, Frequencies of the two major functional CYP2D61 and CYP2D62 alleles and the CYP2D6*5 null allele were similar to most populations world-wide, The alleles CYP2D63 and *9, absent in Asians , were not found in Mapuches. The CYP2D64 allelic group, uncommon in Asian populations, had a low frequency in Mapuches (0.036), However, t he CYP2D610 allele (Ch1, Ch2 and J), highly frequent in Asians (0.33- 0.50), had a very low frequency (0.018) in oar study population. In ad dition, the presence of the common Chinese 44 kb XbaI fragment of CYP2 D6 (0.19-0.31 in Asians) was not detected in South-Amerindians. Intere stingly, high frequencies for the rare m2 and Val alleles of the CYP1A 1 gene were found in Mapuches (0.821 and 0.91, respectively), and the rare Val/m2 haplotype was significantly higher in Mapuches (0.748) tha n in Asians (0.24) (P < 0.01), The frequency of this haplotype in Mapu ches is the highest frequency reported to date. The population studied was in Hardy-Weinberg equilibrium for these polymorphisms. The major differences between Mapuches and Asians were for CYP2D610 and CYP1A1 allelic frequencies, as web as the absence of the common Chinese 44 kb XbaI fragment of CYP2D6. These differences might be interpreted as a consequence of genetic drifts caused by a founder effect in the settle ment of South-Amerindians, or genetic selection caused by dietary or e nvironmental factors. Pharmacogenetics 8:343-351 (C) 1998 Lippincott-R aven Publishers.