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


CONCLUSIONS
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.
Divisão de Farmacologia, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro, 20231-050, Brazil.
Daniela D
DD
Vargens
Lucas
L
Almendra
Cláudio J
CJ
Struchiner
Guilherme
G
Suarez-Kurtz
D000483:Alleles; D044383:Black People / Q000235:genetics; D001938:Brazil; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D044469:Racial Groups / Q000235:genetics; D044465:White People / Q000235:genetics
C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins