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, chi(2) 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, chi(2) 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.
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, chi(2) 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, chi(2) 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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