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

Perini, J.A.; Vargens, Daniela D.; Santana, I.S.C.; Moriguchi, E.H.; Ribeiro-dos-Santos, A.K.C.; Tsutsumi, M.; Suarez‐Kurtz, Guilherme

doi:10.1590/s0100-879x2009007500004

Cited by 2 publications

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“…Having recently shown that the accuracy of NAT2 acetylator phenotype inference based on either rs1495741 or paired NAT2 SNPs varies markedly across continental populations [2], we decided to examine whether the conclusions proposed by Hein and Doll apply to distinct non-European cohorts, including Mozambicans from southwest Africa (n = 102), Japanese (n = 87), Guarani-Amerindians living in Brazil (n = 88), and non-Amerindian Brazilians, self-identified as white (n = 136), brown (n = 107) or black (n = 118). These cohorts have been described in previous studies from our laboratories, which provide information on institutional review boards and informed consent [2,3].…”

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Accuracy of NAT2 SNP Genotyping Panels to Infer Acetylator Phenotypes in African, Asian, Amerindian and Admixed Populations

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Accuracy of NAT2 SNP Genotyping Panels to Infer Acetylator Phenotypes in African, Asian, Amerindian and Admixed Populations

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“…We extended our studies on the INCL cohort to explore the association of other variables with warfarin dose requirements (SuarezKurtz et al, 2009), and reported that the inclusion of INR/dose as a covariate in regression modeling of the stable warfarin dose leads to a novel algorithm with greater predictive power (R 2 = 60%; Figure 5). The most informative model retained the same covariates previously identified as associated with stable warfarin weekly dose in this cohort (age, weight, treatment indication, co-medication with amiodarone, or simvastatin, VKORC1 and CYP2C9 genotypes) but included also an INR/dose term.…”

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Pharmacogenetics in the Brazilian Population

Suarez‐Kurtz¹

Racial Identities, Genetic Ancestry, and Health in South America

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Brazil is the fifth largest country in the world and its present population, in excess of 190 million, is highly heterogeneous, as a result of centuries of admixture between Amerindians, Europeans, and Sub-Saharan Africans. The estimated individual proportions of biogeographical ancestry vary widely and continuously among Brazilians: most individuals, irrespective of self-identification as White, Brown or Black -the major categories of the Brazilian Census "race/color" system -have significant degrees of European and African ancestry, while a sizeable number display also Amerindian ancestry. These features have important pharmacogenetic (PGx) implications: first, extrapolation of PGx data from relatively well-defined ethnic groups is clearly not applicable to the majority of Brazilians; second, the frequency distribution of polymorphisms in pharmacogenes (e.g., CYP3A5, CYP2C9, GSTM1, ABCB1, GSTM3, VKORC, etc) varies continuously among Brazilians and is not captured by race/color self-identification; third, the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of PGx studies in order to avoid spurious conclusions based on improper matching of study cohorts. The peculiarities of PGx in Brazilians are illustrated with data for different therapeutic groups, such as anticoagulants, HIV protease inhibitors and non-steroidal antinflammatory drugs, and the challenges and advantages created by population admixture for the study and implementation of PGx are discussed. PGx data for Amerindian groups and Brazilian-born, first-generation Japanese are presented to illustrate the rich diversity of the Brazilian population. Finally, I introduce the reader to the Brazilian Pharmacogenetic Network or Refargen 1 , a nation-wide consortium of research groups, with the mission to provide leadership in PGx research and education in Brazil, with a population health impact.Keywords: biogeographical ancestry, Brazilian pharmacogenetic network, population admixture, warfarin, HIV protease inhibitors, non-steroidal anti-inflammatory drugs databases, in consonance with either the first or the second models described by Pena (2007). However, both models are poor descriptors of admixed populations, since genetic admixture is best modeled as a continuous variable, consistent with the VMG paradigm Pena, 2006, 2007;Pena, 2007). The individual uniqueness that is central to this paradigm implies that "each person must be treated as an individual… rather than as an exemplar of a race" (Patrinos, 2004) or in the words of McLeod (2007) "data from ethnic groups will not be as useful as analysis of individuals patients. While knowledge of ethnic differences may be relevant to much of the world's population, its usefulness is significantly limited in situations of extensive genetic mixing". With increasing global migration, admixture gains relevance as an additional challenge to the successful worldwide implementation of PGx in clinical practice. From this perspective, the Brazilian population, ...

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

Cited by 2 publications

References 6 publications

Accuracy of NAT2 SNP Genotyping Panels to Infer Acetylator Phenotypes in African, Asian, Amerindian and Admixed Populations

Accuracy of NAT2 SNP Genotyping Panels to Infer Acetylator Phenotypes in African, Asian, Amerindian and Admixed Populations

Pharmacogenetics in the Brazilian Population

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