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Genetic polymorphisms of CYP2D6, CYP1A1 and CYP2E1 in the South-Amerindian population of Chile

1998; Lippincott Williams & Wilkins; Volume: 8; Issue: 4 Linguagem: Inglês

10.1097/00008571-199808000-00008

1473-561X

Sebasti n Mu oz, Valeska Vollrath, Mar a P a Vallejos, Juan Francisco Miquel, Carmen Covarrubias, Alejandro Raddatz, Jos Chianale,

Eicosanoids and Hypertension Pharmacology

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 Xbal 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 Xbal 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.