Genetic Diversity of Drug-Related Genes in Native Americans of the Brazilian Amazon

Fernandes, Marianne Rodrigues; Rodrigues, Juliana Carla Gomes; Maroñas, Olalla; Latorre‐Pellicer, Ana; Cruz, Raquel; Guerreiro, João Farias; Burbano, Rommel Rodrı́guez; Assumpção, Paulo Pimentel de; Ribeiro-dos-Santos, Ândrea; Santos, Sidney Emanuel Batista dos; Carracedo, Ángel; Santos, Ney Pereira Carneiro dos

doi:10.2147/pgpm.s274741

Cited by 3 publications

(3 citation statements)

References 54 publications

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“…When DNA is exposed to radiation, DNA double-strand breaks occur, which favors a response to this damage, such as cellular radioresistance [46,47]. This was the first exome study to examine genes associated with the response to radiotherapy in indigenous populations, a group that is usually underrepresented in genetic studies, especially in precision medicine [48].…”

Section: Discussionmentioning

confidence: 99%

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population

de Lima,

de Castro,

Aguiar

et al. 2024

JPM

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Radiotherapy is focused on the tumor but also reaches healthy tissues, causing toxicities that are possibly related to genomic factors. In this context, radiogenomics can help reduce the toxicity, increase the effectiveness of radiotherapy, and personalize treatment. It is important to consider the genomic profiles of populations not yet studied in radiogenomics, such as the indigenous Amazonian population. Thus, our objective was to analyze important genes for radiogenomics, such as ATM, TGFB1, RAD51, AREG, XRCC4, CDK1, MEG3, PRKCE, TANC1, and KDR, in indigenous people and draw a radiogenomic profile of this population. The NextSeq 500® platform was used for sequencing reactions; for differences in the allelic frequency between populations, Fisher’s Exact Test was used. We identified 39 variants, 2 of which were high impact: 1 in KDR (rs41452948) and another in XRCC4 (rs1805377). We found four modifying variants not yet described in the literature in PRKCE. We did not find any variants in TANC1—an important gene for personalized medicine in radiotherapy—that were associated with toxicities in previous cohorts, configuring a protective factor for indigenous people. We identified four SNVs (rs664143, rs1801516, rs1870377, rs1800470) that were associated with toxicity in previous studies. Knowing the radiogenomic profile of indigenous people can help personalize their radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population

de Lima,

de Castro,

Aguiar

et al. 2024

JPM

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“…However, some population groups remain underrepresented in these types of investigations, such as Native American populations. Recently, some efforts have been made to include genetic information about allelic frequencies of Native American populations and their influence on susceptibility to diseases, such as severe forms of COVID-19 [ 23 ], psychological disorders [ 24 ], oncological diseases [ 25 , 26 ], and also on different types of pharmacological treatments [ 12 , 13 , 27 , 28 ]. Most of these studies are focused on one or a few group of genes.…”

Section: Discussionmentioning

confidence: 99%

“…These populations are extremely underrepresented in genetic research. In parallel, some studies have already demonstrated that Amerindian groups have distinct genetic profiles concerning pharmacogenomic biomarkers widely used in clinical practice [ 12 , 13 ], which further reinforces the need for their inclusion in pharmacogenomic studies.…”

Section: Introductionmentioning

confidence: 94%

Pharmacogenomic Profile of Amazonian Amerindians

Rodrigues

Fernandes

Ribeiro-dos-Santos

et al. 2022

JPM

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Given the role of pharmacogenomics in the large variability observed in drug efficacy/safety, an assessment about the pharmacogenomic profile of patients prior to drug prescription or dose adjustment is paramount to improve adherence to treatment and prevent adverse drug reaction events. A population commonly underrepresented in pharmacogenomic studies is the Native American populations, which have a unique genetic profile due to a long process of geographic isolation and other genetic and evolutionary processes. Here, we describe the pharmacogenetic variability of Native American populations regarding 160 pharmacogenes involved in absorption, distribution, metabolism, and excretion processes and biological pathways of different therapies. Data were obtained through complete exome sequencing of individuals from 12 different Amerindian groups of the Brazilian Amazon. The study reports a total of 3311 variants; of this, 167 are exclusive to Amerindian populations, and 1183 are located in coding regions. Among these new variants, we found non-synonymous coding variants in the DPYD and the IFNL4 genes and variants with high allelic frequencies in intronic regions of the MTHFR, TYMS, GSTT1, and CYP2D6 genes. Additionally, 332 variants with either high or moderate (disruptive or non-disruptive impact in protein effectiveness, respectively) significance were found with a minimum of 1% frequency in the Amazonian Amerindian population. The data reported here serve as scientific basis for future design of specific treatment protocols for Amazonian Amerindian populations as well as for populations admixed with them, such as the Northern Brazilian population.

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Characterization of DNA Polymerase Genes in Amazonian Amerindian Populations

Cohen-Paes

Alcântara

Menezes

et al. 2022

Genes

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Due to their continuing geographic isolation, the Amerindian populations of the Brazilian Amazon present a different genetic profile when compared to other continental populations. Few studies have investigated genetic variants present in these populations, especially in the context of next-generation sequencing. Knowledge of the molecular profile of a population is one of the bases for inferences about human evolutionary history, in addition, it has the ability to assist in the validation of molecular biomarkers of susceptibility to complex and rare diseases, and in the improvement of specific precision medicine protocols applied to these populations and to populations with high Amerindian ancestry, such as Brazilians. DNA polymerases play essential roles in DNA replication, repair, recombination, or damage repair, and their influence on various clinical phenotypes has been demonstrated in the specialized literature. Thus, the aim of this study is to characterize the molecular profile of POLA1, POLE, POLG, POLQ, and REV3L genes in Amerindian populations from the Brazilian Amazon, comparing these findings with genomic data from five continental populations described in the gnomAD database, and with data from the Brazilian population described in ABraOM. We performed the whole exome sequencing (WES) of 63 Indigenous individuals. Our study described for the first time the allele frequency of 45 variants already described in the other continental populations, but never before described in the investigated Amerindian populations. Our results also describe eight unique variants of the investigated Amerindians populations, with predictions of moderate, modifier and high clinical impact. Our findings demonstrate the unique genetic profile of the Indigenous population of the Brazilian Amazon, reinforcing the need for further studies on these populations, and may contribute to the creation of public policies that optimize not only the quality of life of this population, but also of the Brazilian population.

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Genetic Diversity of Drug-Related Genes in Native Americans of the Brazilian Amazon

Cited by 3 publications

References 54 publications

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population

Pharmacogenomic Profile of Amazonian Amerindians

Characterization of DNA Polymerase Genes in Amazonian Amerindian Populations

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