Pharmacogenetic polymorphisms in Brazilian-born, first-generation Japanese descendants

Brazil hosts the largest Japanese community outside Japan, estimated at 1.5 million individuals, one third of whom are first-generation, Brazilian-born with native Japanese parents. This large community provides a unique opportunity for comparative studies of the distribution of pharmacogenetic polymorphisms in native Japanese versus their Brazilian-born descendants. Functional polymorphisms in genes that modulate drug disposition (CYP2C9, CYP2C19 and GSTM3) or response (VKORC1) and that differ significantly in frequency in native Japanese versus Brazilians with no Japanese ancestry were selected for the present study. Healthy subjects (200 native Japanese and 126 first-generation Japanese descendants) living in agricultural colonies were enrolled. Individual DNA was genotyped using RFLP (GSTM3*A/B) or TaqMan Detection System assays (CYP2C9*2 and *3; CYP2C19*2 and *3; VKORC1 3673G>A, 5808T>G, 6853G>C, and 9041G>A). No difference was detected in the frequency of these pharmacogenetic polymorphisms between native Japanese and first-generation Japanese descendants. In contrast, significant differences in the frequency of each polymorphism were observed between native or first-generation Japanese and Brazilians with no Japanese ancestry. The VKORC1 3673G>A, 6853G>C and 9041G>A single nucleotide polymorphisms were in linkage disequilibrium in both native and first-generation Japanese living in Brazil. The striking similarity in the frequency of clinically relevant pharmacogenetic polymorphisms between Brazilian-born Japanese descendants and native Japanese suggests that the former may be recruited for clinical trials designed to generate bridging data for the Japanese population in the context of the International Conference on Harmonization

Monomorphic and polymorphic enzyme genetic markers of the Waiãpi Indians of Amapá and of inhabitants of Manaus, Amazonas

One hundred nineteen Waiãpi Indians and 348 inhabitants of Manaus, Amazonas, were tested using nine enzyme genetic systems in the first population and two in the second. The Waiãpi showed some marked differences compared to South American Indian averages in ACP*A (1% vs. 14 ± 9%), GLO1*1 (9% vs. 30 ± 14%) and ESD*1 (99.6% vs. 70 ± 17%), while ESD*1 and CA2*1 prevalences in the Manaus population were within the range previously found in the northern region of Brazil (ESD*1: 85% vs. 80-94%; CA2*1: 98% vs. 89-99.8%). The almost identical frequencies obtained for these two markers in this population, when the sample was subdivided according to skin color, suggest that such morphological classifications have little value in this region. Genetic distances between the Waiãpi and other tribes, obtained using these and other genetic markers, showed good parallelism with the geographical distances which separate these Indians from the other groups considered.<br>Um total de 119 índios Waiãpi e 348 habitantes de Manaus, Amazonas, foram testados usando nove sistemas genéticos enzimáticos na primeira população e dois na segunda. Os Waiãpi mostraram algumas diferenças marcantes quanto às médias dos indígenas sul-americanos em ACP*A (1% vs. 14 ± 9%), GLO1*1 (9% vs. 30 ± 14%) e ESD*1 (99,6% vs. 70 ± 17%), enquanto as prevalências de ESD*1 e CA2*1 na população de Manaus mostraram-se dentro do intervalo encontrado previamente na região norte do Brasil (ESD*1: 85% vs. 80-94%; CA2*1: 98% vs. 89-99.8%). As freqüências quase idênticas obtidas para esses dois marcadores nesta população, quando a amostra foi subdividida de acordo com a cor da pele, sugerem que tais classificações morfológicas têm pouco valor nesta região. Distâncias genéticas entre os Waiãpi e outras tribos, obtidas usando esses e outros marcadores genéticos, mostraram bom paralelismo com as distâncias geográficas que separam esses índios dos outros grupos considerados