title: Genetic polymorphisms of CYP2D6, CYP1A1 and CYP2E1 in the South-Amerindian population of Chile.
abstract: Polymorphisms of cytochrome P450 genes show pronounced interethnic variation and have not been previously studied in the South-Amerindian population, which probably has an Asian origin. Therefore, a similar distribution of allelic and haplotype frequencies of cytochrome P450 genes to Asian populations might be expected in South-Amerindians. We analysed the allelic frequencies and haplotype distribution for CYP2D6, CYP1A1 and CYP2E1 genes in the South-Amerindian population of Chile (Mapuche, n = 84) by Southern blot or polymerase chain reaction-restriction fragment length polymorphism. Similar allelic frequencies and haplotype distribution for the CYP2E1 gene between Mapuches and Asian populations were observed. Frequencies of the two major functional CYP2D6*1 and CYP2D6*2 alleles and the CYP2D6*5 null allele were similar to most populations world-wide. The alleles CYP2D6*3 and *9, absent in Asians, were not found in Mapuches. The CYP2D6*4 allelic group, uncommon in Asian populations, had a low frequency in Mapuches (0.036). However, the CYP2D6*10 allele (Ch1, Ch2 and J), highly frequent in Asians (0.33-0.50), had a very low frequency (0.018) in our study population. In addition, the presence of the common Chinese 44 kb XbaI fragment of CYP2D6 (0.19-0.31 in Asians) was not detected in South-Amerindians. Interestingly, high frequencies for the rare m2 and Val alleles of the CYP1A1 gene were found in Mapuches (0.821 and 0.91, respectively), and the rare Val/m2 haplotype was significantly higher in Mapuches (0.748) than in Asians (0.24) (P < 0.01). The frequency of this haplotype in Mapuches 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 CYP2D6*10 and CYP1A1 allelic frequencies, as well 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 settlement of South-Amerindians, or genetic selection caused by dietary or environmental factors.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago.
authors.forename: S
authors.initials: S
authors.lastname: Muñoz
authors.forename: V
authors.initials: V
authors.lastname: Vollrath
authors.forename: M P
authors.initials: MP
authors.lastname: Vallejos
authors.forename: J F
authors.initials: JF
authors.lastname: Miquel
authors.forename: C
authors.initials: C
authors.lastname: Covarrubias
authors.forename: A
authors.initials: A
authors.lastname: Raddatz
authors.forename: J
authors.initials: J
authors.lastname: Chianale
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002677:Chile; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D007199:Indians, South American / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6