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Pharmacogenetic polymorphisms in Brazilian-born, first-generation Japanese descendants
J A Perini1, D D Vargens, I S C Santana
1Divisão de Farmacologia, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brasil.
Summary
Pharmacogenetic polymorphisms in drug-metabolizing enzymes (CYP2C9, CYP2C19, GSTM3) and drug targets (VKORC1) showed similar frequencies between native Japanese and their Brazilian-born descendants. These findings support using Japanese descendants in clinical trials.
Area of Science:
- Pharmacogenetics
- Population Genetics
- Drug Metabolism
Background:
- Brazil has the largest Japanese diaspora, offering a unique setting for genetic studies.
- Understanding pharmacogenetic variations is crucial for personalized medicine and drug development.
Purpose of the Study:
- To compare the frequencies of key pharmacogenetic polymorphisms in native Japanese and their Brazilian-born descendants.
- To assess the genetic similarity between these groups and Brazilians of non-Japanese ancestry.
- To evaluate the potential of Japanese descendants in Brazil for clinical trials.
Main Methods:
- Genotyping of functional polymorphisms in CYP2C9, CYP2C19, GSTM3, and VKORC1 genes using RFLP and TaqMan assays.
- Study population included 200 native Japanese and 126 first-generation Japanese descendants in Brazil.
- Comparison of allele frequencies between Japanese descendants, native Japanese, and Brazilians without Japanese ancestry.
Main Results:
- No significant differences in pharmacogenetic polymorphism frequencies were found between native Japanese and their Brazilian-born descendants.
- Significant differences were observed between Japanese groups and Brazilians of non-Japanese ancestry.
- VKORC1 polymorphisms (3673G>A, 6853G>C, 9041G>A) were in linkage disequilibrium in both Japanese groups in Brazil.
Conclusions:
- Brazilian-born Japanese descendants maintain genetic profiles similar to native Japanese regarding key pharmacogenetic polymorphisms.
- This genetic similarity supports the use of Japanese descendants in Brazil for clinical trials requiring Japanese population data.
- Findings have implications for international drug development and regulatory harmonization (ICH).
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