Open Access Highly Accessed Research article

CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Paulo CJL Santos, Renata AG Soares, Diogo BG Santos, Raimundo M Nascimento, George LLM Coelho, José C Nicolau, José G Mill, José E Krieger and Alexandre C Pereira*

BMC Medical Genetics 2011, 12:13  doi:10.1186/1471-2350-12-13

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Previous studies of ABCB1 and CYP2C19 polymorphisms in Brazilians

Guilherme Suarez-Kurtz   (2011-10-18 15:20)  Instituto Nacional de Câncer email

Santos et al. [1] reported the distribution of CYP2C19 and ABCB1 polymorphisms in Brazilians, and discussed their results with respect to European, Asian and African populations, but made no reference to previously published studies in the Brazilian population. This is particularly disconcerting in the case of the ABCB1 3435C>T SNP, since this polymorphism was first studied in Brazilians in 2002 [2]! Several subsequent articles, listed in PubMed and in the internet site of Refargen, the Brazilian Pharmacogenetics Network (, examined the frequency of the 3435C>T and other ABCB1 SNPs (e.g. 1236C>T and 2677G>T/A) and haplotypes in different strata of the Brazilian population [3 - 5]. The results of Santos et al. [1] for ABCB1 3435C>T in non-Amerindian sub-groups reproduce very closely these previously published data. For example, the frequency of the 3435T allele is 0.33 in the “African descent” cohort of Santos et al. [1]] versus 0.31 in self-identified black individuals in our study [5]. In this study we demonstrated that, among Brazilians, the odds of having the 3435T allele decreases with the increase of the individual proportion of the “African component of ancestry”. This provided a convincing explanation for the lower frequency of the 3435T allele in self-identified black Brazilians, compared to sub-Saharan Africans, since the estimated proportion of African ancestry in black Brazilians averages only 0.46 - 0.51 [6, 7]. Santos et al. [1] adopted this interpretation for the low frequency of ABCB1 3435T allele in their “African descent” cohort, but did not find it fit to mention our article, published in 2008 [5].
The frequency of the CYP2C19*2 and *3 polymorphisms in different strata of the Brazilian population was also publicly available [8] before Santos et al. submitted the final version of their manuscript ( Indeed, researchers associated with Refargen assessed the impact of biogeographical ancestry, self-reported “race/color” and geographical origin on the frequency distribution of CYP2C19*2, *3 and *17 in a representative cohort of the Brazilian population (n=1,034). Multinomial log-linear modeling revealed that geographical region and/or self-reported color/race had no effect on the frequency distribution of the CYP219 variant alleles [8]. The data reported by Santos et al. [1] for CYP2C19*2 in non-Amerindian sub-groups confirmed these findings, However a discrepancy is observed in relation to CYP2C19*17, which is more frequent in “African descent” than in “European descent” and “Mulatto” sub-groups studied by Santos et al [1]. These authors did not took notice of this discrepancy, but we alluded to it - duly quoting Santos et al. [1] - in a recent article on the distribution of polymorphisms in the CYP2C cluster among Amerindian populations [9] .
The approach adopted by Santos et al [1] to ignore previously published data for the ABCB1 3435C>T and CYP2C19 polymorphisms in the Brazilian population, might induce the reader to assume (wrongly) that these authors were the first to study the distribution of these clinically relevant variants among Brazilians. This assumption might be erroneously extended to other pharmacogenes, e.g. VKORC1, which Santos et al. [1] present as a distinct example of interethnic diversity using data from multinational studies [10, 11] – of which, incidentally I am co-author - but again ignoring results for their fellow countrymen. Had Santos et al. considered our articles [12, 13] they might have qualified their statement that “the contribution of VKORC1 toward (warfarin) dose requirements is higher in whites than non-whites”. We presented evidence that warfarin dose algorithms, having a VKORC1 polymorphism as the most important co-variate, perform equally well in white and black Brazilians.
A final consideration concerns “ethnic/racial” categorization: Santos et al. [1] stated that their study population was “separated in self-identified sub-groups according to ethnicity, as Caucasian descent, African descent, or Mulattos (considered racially mixed subjects)”. I find it highly unlikely that the average Brazilian would self-identify as being of “Caucasian descent” or “African descent”. According to the “racial/ethnic” categorization used by the Brazilian Institute of Geography and Statistics (quoted by Santos et al. [1], that relies on self-perception of skin color, over 99% of Brazilians self-identify as Branco (white), Preto (black) or Pardo (meaning brown). Because these “race/color” categories correlate poorly with biogeographical ancestry of Brazilians and because most Brazilians have significant proportions of African and European ancestry, irrespective of the self-perception of “race/color” [6, 14, 15], terms such as “Caucasian descent” or “African descent” are poor descriptors of self-identified white or black Brazilians.


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