Y-linked microsatellites in Amazonian Amerindians applied to ancestry estimates in Brazilian Afro-derived populations.

OBJECTIVES: Proper ancestral populations are required to determine accurate ancestry estimates for Afro-derived Brazilian populations. Herein, we have genotyped Y-STRs in Amazonian Amerindians to determine the ancestral contribution in quilombo remnant communities. METHODS: The frequencies for five Y-chromosome linked microsatellites (DYS19, DYS390, DYS391, DYS392, and DYS393) were characterized in four Amerindian tribes from Brazilian Amazon (Tikúna, Baníwa, Kashinawa, and Kanamarí), and in four quilombo remnants (Mimbó, Sítio Velho, Gaucinha, and São Gonçalo) and two urban populations (Teresina and Jequié) from Northeastern Brazil. We then estimated the male genetic ancestry in each admixed population. Moreover, we performed analysis of molecular variance (AMOVA), FST , haplotype diversity, and principal component analysis. RESULTS: Lower haplotype diversity (h) values were observed for Tikúna compared with other tribes. Quilombo remnants exhibited higher h levels ranging from 0.893 ± 0.027 in Sítio Velho to 0.963 ± 0.033 in São Gonçalo. African ancestry estimates ranged from 0.529 ± 0.027 in Mimbó to 0.602 ± 0.086 in Sítio Velho. Conversely, European contribution was 0.795 ± 0.045 in Teresina and 0.826 ± 0.040 in Jequié. CONCLUSIONS: FST and principal component analysis indicate homogeneity in the male genetic constitution among the quilombo remnants analyzed. Data on Amerindians allowed accurate ancestry estimates, which indicated a higher African contribution, followed by a considerable European contribution for these quilombo remnants.

Does celiac disease occur in Afro-derived Brazilian populations?

BACKGROUND: Celiac disease is an autoimmune disorder that occurs in genetically susceptible individuals in whom the ingestion of dietary gluten induces intestinal mucosa inflammation. Previous studies suggest that celiac disease may either be very rare or underdiagnosed in African and/or African-derived population. AIM: Determine the prevalence of celiac disease in Sub-Saharan African-derived Brazilian communities using serological screening. SUBJECTS AND METHODS: Inhabitants from 10 African-derived communities from Northeastern of Brazil were screened for celiac disease. All sera were tested for endomysial class IgA antibody using indirect immunofluorescence. RESULTS: No positive test for IgA-endomysial was observed in the 860 individuals tested. CONCLUSION: Our data suggests a low prevalence of celiac disease in African-derived Brazilian populations.

Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations.

BACKGROUND: N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of NAT2 polymorphism is different among these three ethnic groups. RESULTS: Overall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians. CONCLUSIONS: Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 gene-environment effects in admixed populations.

Y-chromosome STR haplotypes in a sample from São Paulo State, southeastern Brazil.

POPULATION: Unrelated males from the São Paulo State, Brazil (n=617).

Associação do polimorfismo de IL-13 (+1398A/G) com a asma e a ancestralidade genômica / Association of IL-13 (+1398A/G) gene polymorphisms with asthma and genomic ancestry

Introdução: A asma é uma doença complexa, resultante da interação entre fatores genéticos e ambientais. A expressão aumentada de genes relacionados à inflamação define as alterações celulares e estruturais do aparelho respiratório, enquanto o meio ambiente modula os diferentes fenótipos asmáticos. Os produtos dessas células envolvidos na inflamação incluem citocinas, como a interleucina13 (IL-13), que está relacionada com a síntese direta de IgE, imunoglobulina essencial na patogênese da asma. Há divergências entre a prevalência da asma e o grupo étnico estudado, desta forma, o uso de Marcadores Informativos de Ancestralidade (AIM ­ Ancestry Informative Markers) possibilita a caracterização da ancestralidade genômica de diferentes populações. Objetivos: Verificar a associação entre polimorfismos do gene IL-13R com a ancestralidade genômica e a asma em uma população no sul da Bahia. Métodos: Foram genotipadas 320 amostras, sendo 114 casos, e 206 controles, utilizando o método de PCR e PCR/RFLP em sete AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM e PV92) que apresentam elevado diferencial de frequência alélica entre africanos, ameríndios e europeu, e um polimorfismo no receptor de IL-13 (IL-13RA1). Resultados: Os resultados desse estudo mostraram que a maior contribuição foi ameríndia, tanto para os casos (37,42%), como para os controles (50,52%), demonstrando que há diferenças nas contribuições étnicas das amostras da região estudada. O polimorfismo no receptor de IL-13 (IL- 13RA1) apresentou associação significativa com rinite e história familiar. Conclusões: A heterogeneidade da composição étnica das amostras pode ter influenciado na não associação das duas variáveis: níveis de IgE sérico e histórico familiar, e a presença do polimorfismo no receptor da IL-13RA1, e aponta a necessidade de realização do controle genômico.

Introduction: Asthma is a complex disease resulting from the interaction between genetic and environmental factors. Increased expression of inflammatory genes defines cellular and structural changes in the respiratory tract, while the environment modulates the different asthmatic phenotypes. Cell products involved in inflammation include cytokines, such as interleukin-13 (IL-13), which is related to the direct synthesis of IgE, an immunoglobulin that plays a key role in the pathogenesis of asthma. Because there is divergence of asthma prevalence between different ethnic groups, the use of ancestry informative markers (AIMs) allows for the characterization of genomic ancestry in different populations. Objectives: To examine the association of IL-13R gene polymorphisms with genomic ancestry and asthma in a population from the south of Bahia. Methods: A total of 320 samples, 114 cases and 206 controls, were genotyped using PCR and PCR/RFLP methods for 7 AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM, and PV92) that showed a high allele frequency differential between Africans, Amerindians, and Europeans and 1 polymorphism in the IL-13 receptor (IL-13RA1). Results: Amerindian ancestry provided the greatest contribution in both cases (37.42%) and controls (50.52%), indicating that there are differences in the ethnic contribution of the samples from the study region. The IL-13 receptor (IL-13RA1) polymorphism was significantly associated with rhinitis and family history. Conclusions: Heterogeneity in the ethnic composition of the samples may have influenced the non-association of serum IgE levels and family history with the presence of IL-13RA1 receptor polymorphism, and the results point to the need for genomic control.

TNF microsatellite alleles in Brazilian Chagasic patients.

To evaluate the tumor necrosis factor (TNF) a-e microsatellite polymorphism in Chagasic patients, we studied 162 patients stratified according to the major clinical variants (cardiac, digestive, digestive plus cardiac, and indeterminate forms) and 221 healthy controls. TNF microsatellite alleles were typed using genomic DNA amplified with specific primers. Statistical analyses were performed using the GENEPOP and ARLEQUIN softwares and the two-tailed Fisher exact test. The TNFa2, TNFa7, TNFa8, TNFb2, TNFb4, TNFd5, TNFd7, and TNFe2 alleles were overrepresented, whereas the TNFb7 and TNFd3 alleles were underrepresented when clinical variants of Chagas' disease or the patient group as a whole were compared with controls. Twelve TNF haplotypes were associated with susceptibility to or protection against Chagas' disease, considered as a whole or stratified into clinical variants. Many of these haplotypes encompassed the above-described susceptibility/protective alleles. These results indicate that the TNF chromosomal region is relevant for Chagas' disease development.

CCR5D32 mutation in three Brazilian populations of predominantly Sub-Saharan African ancestry

This study reports the frequencies of the CCR5D32 mutation of the beta-chemokine 5 gene and discusses the possible effects of past and recent gene flow in three quilombo remnants (Brazilians communities with anthropological African ancestry whose ancestors were escaped slaves): Rio das Rãs, Mocambo, and São Gonçalo in the northeastern region of Brazil. The CCR5D32 allele frequency of the Mocambo population was significantly higher (5.6 percent) than that found in the Rio das Rãs (1 percent) and São Gonçalo (0.9 percent) populations. These differences may reflect different proportions of parental populations in the founders individuals, a founder-effect and/or different histories of inter-ethnic contact. The frequency of the CCR5D32 allele in the Mocambo sample is similar to that found in those urban Brazilian populations which have a large amount of European genetic input, indicating a European contribution to the gene pool of this population and suggesting that, perhaps since its foundation, Mocambo has had a high level of admixture or experienced a founder-effect.