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Distribution of the GNB3 825C>T polymorphism among Brazilians: impact of population structure

  • Pharmacogenetics
  • Published:
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Abstract

Objective

To describe the impact of population admixture on the distribution of the GNB3 825C>T polymorphism in the heterogeneous Brazilian population.

Methods

Individual DNA from 236 healthy Brazilians, self-identified as White, Intermediate and Black, was genotyped for a set of insertion/deletion polymorphisms that have been previously validated as ancestry informative markers (AIMs). The GNB3 825C>T polymorphism was detected by PCR-RFLP. Non-linear logistic regression modeling was applied to describe the association between the GNB3 825C>T polymorphisms and the African component of ancestry (ACA) estimated by the AIMs.

Results

The GNB3 825C>T allele and genotype distribution differed significantly across the three self-reported groups (P < 0.0001, χ2 test), with a trend for increasing frequency of both the GNB3 825T allele and the TT genotype from White to Intermediate to Black individuals (P < 0.0001, χ2 test for trend in proportions). Non-linear logistic regression showed that the odds of having the GNB3 825C>T allele increase monotonically (P < 0.0001, Wald statistics) with increasing ACA throughout the ACA range (0.136–0.897) observed in the overall population sample, irrespective of “racial/color” self-identification.

Conclusion

The present data on the GNB3 825C>T polymorphism support the notion that interethnic admixture, which is a source of spurious genotype–phenotype associations in pharmacogenetic/-genomic studies, must be dealt with as a continuous variable, rather than proportioned in arbitrary sub-categories for the convenience of data quantification and analysis.

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Acknowledgments

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Swiss Bridge Foundation. The authors declare that the experiments reported in this study comply with the current laws of Brazil.

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Authors and Affiliations

  1. Divisão de Farmacologia, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro, 20231-050, Brazil

    Daniela D. Vargens, Lucas Almendra & Guilherme Suarez-Kurtz

  2. Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

    Cláudio J. Struchiner

Authors
  1. Daniela D. Vargens
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  2. Lucas Almendra
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  3. Cláudio J. Struchiner
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  4. Guilherme Suarez-Kurtz
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Correspondence to Guilherme Suarez-Kurtz.

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Vargens, D.D., Almendra, L., Struchiner, C.J. et al. Distribution of the GNB3 825C>T polymorphism among Brazilians: impact of population structure. Eur J Clin Pharmacol 64, 253–256 (2008). https://doi.org/10.1007/s00228-007-0413-2

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  • DOI: https://doi.org/10.1007/s00228-007-0413-2

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