Epidemiological-molecular profile of variants associated with type 2 diabetes mellitus in indigenous populations from the Brazilian Amazon.

AIMS: While lifestyle factors are strongly associated with Type 2 diabetes (T2DM), genetic characteristics also play a role. However, much of the research on T2DM genetics focuses on European and Asian populations, leaving underrepresented groups, such as indigenous populations with high diabetes prevalence, understudied. METHODS: We characterized the molecular profile of 10 genes involved in T2DM risk through complete exome sequencing of 64 indigenous individuals belonging to 12 different Amazonian ethnic groups. RESULTS: The analysis revealed 157 variants, including four exclusive variants in the indigenous population located in the NOTCH2 and WFS1 genes with a modifier or moderate impact on protein effectiveness. Furthermore, a high impact variant in NOTCH2 was also found. Additionally, the frequency of 10 variants in the indigenous group showed significant differences when compared to other global populations that were evaluated. CONCLUSION: Our study identified 4 novel variants associated with T2DM in the NOTCH2 and WFS1 genes in the Amazonian indigenous populations we studied. In addition, a variant with a high predicted impact in NOTCH2 was also observed. These findings represent a valuable starting point for conducting further association and functional studies, which could help to improve our understanding of the unique characteristics of this population.

African gene flow to north Brazil as revealed by HBB*S gene haplotype analysis.

Haplotypes linked to the HBB*S gene were analyzed in a sample of 260 chromosomes of Brazilian sickle cell anemia patients from the population of Belém, state of Pará, to evaluate if the present-day haplotype frequencies correlate as well as expected with historical information on the geographic origin of African slaves sent directly to Northern Brazil. The HBB*S gene haplotype distribution (66% Bantu, 21.8% Benin, 10.9% Senegal, and 1.3% Cameroon) is in agreement with those observed for other Brazilian populations regarding the highest proportion of the Bantu type, followed by the Benin type, but it differs significantly concerning the Senegal type as this haplotype is rare or absent in samples from other Brazilian regions already studied. In addition, our results are in accordance with historical records that establish that about 90% of the slaves sent to Northern Brazil were from Angola, Congo, and Mozambique, where the Bantu haplotype predominates, in contrast to 10% of slaves from Senegambia, Guine-Bissau, and Cape Verde, where the Senegal haplotype is the most common. On the other hand, the observed frequency of the Benin haplotype in Belém was much higher than that expected by historical data. This fact corroborates the suggestion that the high prevalence of the Benin type in Belém is due to domestic slave trade and later internal migrations, mainly from the Northeast, since there are no historical records of direct slave trade from Central West Africa to North Brazil.