Navegando por Autor "Assumpção, Paulo Pimentel de"
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Artigo Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil(2020-04-15) Rodrigues, Juliana Carla Gomes; Souza, Tatiane Piedade de; Pastana, Lucas Favacho; Santos, André Maurício Ribeiro dos; Fernandes, Marianne Rodrigues; Pinto, Pablo; Wanderley, Alayde Vieira; Souza, Sandro José de; Kroll, José Eduardo; Pereira, Adenilson Leão; Magalhães, Leandro; Mercês, Laís Reis das; Vidal, Amanda Ferreira; Vinasco-Sandoval, Tatiana; Cavalcante, Giovanna Chaves; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Ribeiro-dos-Santos, Ândrea; Santos, Sidney; Santos, Ney Pereira Carneiro dosIntroduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. Conclusion Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.Artigo Identification of variants (rs11571707, rs144848, and rs11571769) in the BRCA2 gene associated with hereditary breast cancer in indigenous populations of the brazilian Amazon(MDPI AG, 2021-01-22) Dobbin, Elizabeth Ayres Fragoso; Medeiros, Jéssyca Amanda Gomes; Costa, Marta Solange Camarinha Ramos; Rodrigues, Juliana Carla Gomes; Guerreiro, João Farias; Kroll, José Eduardo; Souza, Sandro José de; Assumpção, Paulo Pimentel de; Ribeiro-dos-Santos, Ândrea; Santos, Sidney Emanuel Batista dos; Burbano, Rommel Mario Rodríguez; Fernandes, Marianne Rodrigues; Santos, Ney Pereira Carneiro dosEstimates show that 5–10% of breast cancer cases are hereditary, caused by genetic variants in autosomal dominant genes; of these, 16% are due to germline mutations in the BRCA1 and BRCA2 genes. The comprehension of the mutation profile of these genes in the Brazilian population, particularly in Amazonian Amerindian groups, is scarce. We investigated fifteen polymorphisms in the BRCA1 and BRCA2 genes in Amazonian Amerindians and compared the results with the findings of global populations publicly available in the 1000 Genomes Project database. Our study shows that three variants (rs11571769, rs144848, and rs11571707) of the BRCA2 gene, commonly associated with hereditary breast cancer, had a significantly higher allele frequency in the Amazonian Amerindian individuals in comparison with the African, American, European, and Asian groups analyzed. These data outline the singular genetic profiles of the indigenous population from the Brazilian Amazon region. The knowledge about BRCA1 and BRCA2 variants is critical to establish public policies for hereditary breast cancer screening in Amerindian groups and populations admixed with them, such as the Brazilian populationArtigo Incidence of hereditary gastric cancer may be much higher than reported(MDPI AG, 2022-12) Assumpção, Paula Baraúna de; Assumpção, Paulo Pimentel de; Moreira, Fabiano Cordeiro; Santos, Andrea Kely Campos Ribeiro dos; Vidal, Amanda Ferreira; Magalhães, Leandro; Khayat, André Salim; Santos, André Mauricio Ribeiro dos; Cavalcante, Giovanna Chaves; Pereira, Adenilson Leão; Medeiros, Inácio Gomes; Souza, Sandro José de; Burbano, Rommel Mario Rodríguez; Souza, Jorge Estefano Santana de; Santos, Sidney Emanuel Batista dosHereditary gastric cancers (HGCs) are supposed to be rare and difficult to identify. Nonetheless, many cases of young patients with gastric cancer (GC) fulfill the clinical criteria for considering this diagnosis but do not present the defined pathogenic mutations necessary to meet a formal diagnosis of HGC. Moreover, GC in young people is a challenging medical situation due to the usual aggressiveness of such cases and the potential risk for their relatives when related to a germline variant. Aiming to identify additional germline alterations that might contribute to the early onset of GC, a complete exome sequence of blood samples from 95 GC patients under 50 and 94 blood samples from non-cancer patients was performed and compared in this study. The number of identified germline mutations in GC patients was found to be much higher than that from individuals without a cancer diagnosis. Specifically, the number of high functional impact mutations, including those affecting genes involved in medical diseases, cancer hallmark genes, and DNA replication and repair processes, was much higher, strengthening the hypothesis of the potential causal role of such mutations in hereditary cancers. Conversely, classically related HGC mutations were not found and the number of mutations in genes in the CDH1 pathway was not found to be relevant among the young GC patients, reinforcing the hypothesis that existing alternative germline contributions favor the early onset of GC. The LILRB1 gene variants, absent in the world's cancer datasets but present in high frequencies among the studied GC patients, may represent essential cancer variants specific to the Amerindian ancestry's contributions. Identifying non-reported GC variants, potentially originating from under-studied populations, may pave the way for additional discoveries and translations to clinical interventions for GC management. The newly proposed approaches may reduce the discrepancy between clinically suspected and molecularly proven hereditary GC and shed light on similar inconsistencies among other cancer types. Additionally, the results of this study may support the development of new blood tests for evaluating cancer risk that can be used in clinical practice, helping physicians make decisions about strategies for surveillance and risk-reduction interventionsArtigo Molecular profile of variants in CDH1, TP53, PSCA, PRKAA1, and TTN genes related to gastric cancer susceptibility in Amazonian indigenous populations(MDPI AG, 2023-09) Aguiar, Kaio Evandro Cardoso; Oliveira, Izabela De Sousa; Paes, Amanda de Nazaré Cohen; Coelho, Rita de Cássia Calderaro; Vinagre, Lui Wallacy Morikawa Souza; Rodrigues, Juliana Carla Gomes; Santos, André Mauricio Ribeiro dos; Souza, Sandro José de; Santos, Andrea Kely Campos Ribeiro dos; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Santos, Sidney Emanuel Batista dos; Santos, Ney Pereira Carneiro dos; Fernandes, Marianne RodriguesGastric Cancer is a disease associated with environmental and genetic changes, becoming one of the most prevalent cancers around the world and with a high incidence in Brazil. However, despite being a highly studied neoplastic type, few efforts are aimed at populations with a unique background and genetic profile, such as the indigenous peoples of the Brazilian Amazon. Our study characterized the molecular profile of five genes associated with the risk of developing gastric cancer by sequencing the complete exome of 64 indigenous individuals belonging to 12 different indigenous populations in the Amazon. The analysis of the five genes found a total of 207 variants, of which 15 are new in our indigenous population, and among these are two with predicted high impact, present in the TTN and CDH1 genes. In addition, at least 20 variants showed a significant difference in the indigenous population in comparison with other world populations, and three are already associatively related to some type of cancer. Our study reaffirms the unique genetic profile of the indigenous population of the Brazilian Amazon and allows us to contribute to the conception of early diagnosis of complex diseases such as cancer, improving the quality of life of individuals potentially suffering from the diseaseArtigo Molecular profile of variants potentially associated with severe forms of COVID-19 in Amazonian indigenous populations(MDPI AG, 2024-02) Coelho, Rita de Cássia Calderaro; Martins, Carlliane Lima e Lins Pinto; Pastana, Lucas Favacho; Rodrigues, Juliana Carla Gomes; Aguiar, Kaio Evandro Cardoso; Paes, Amanda de Nazaré Cohen; Gellen, Laura Patrícia Albarello; Moraes, Francisco Cezar Aquino de; Calderaro, Maria Clara Leite; Assunção, Letícia Almeida de; Silva, Natasha Monte da; Pereira, Esdras Edgar Batista; Santos, André Mauricio Ribeiro dos; Santos, Andrea Kely Campos Ribeiro dos; Burbano, Rommel Mario Rodriguez; Souza, Sandro José de; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Santos, Sidney Emanuel Batista dos; Fernandes, Marianne Rodrigues; Santos, Ney Pereira Carneiro dosCoronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2. Genome-wide association studies (GWASs) have suggested a strong association of genetic factors with the severity of the disease. However, many of these studies have been completed in European populations, and little is known about the genetic variability of indigenous peoples’ underlying infection by SARS-CoV-2. The objective of the study is to investigate genetic variants present in the genes AQP3, ARHGAP27, ELF5L, IFNAR2, LIMD1, OAS1 and UPK1A, selected due to their association with the severity of COVID-19, in a sample of indigenous people from the Brazilian Amazon in order to describe potential new and already studied variants. We performed the complete sequencing of the exome of 64 healthy indigenous people from the Brazilian Amazon. The allele frequency data of the population were compared with data from other continental populations. A total of 66 variants present in the seven genes studied were identified, including a variant with a high impact on the ARHGAP27 gene (rs201721078) and three new variants located in the Amazon Indigenous populations (INDG) present in the AQP3, IFNAR2 and LIMD1 genes, with low, moderate and modifier impact, respectivelyTese Uma nova assinatura de 13 genes via aprendizagem de máquina para predição de sobrevida de pacientes com carcinoma renal de células clara(Universidade Federal do Rio Grande do Norte, 2022-05-13) Terrematte, Patrick Cesar Alves; Doria Neto, Adrião Duarte; Ferreira, Beatriz Stransky; https://orcid.org/0000-0003-4506-393X; http://lattes.cnpq.br/3142264445097872; https://orcid.org/0000-0002-5445-7327; http://lattes.cnpq.br/1987295209521433; http://lattes.cnpq.br/4283045850342312; Leite, Cicilia Raquel Maia; Araújo, Daniel Sabino Amorim de; http://lattes.cnpq.br/4744754780165354; Assumpção, Paulo Pimentel de; Sakamoto, TetsuPacientes com câncer renal têm sobrevida de 12% em 5 anos em caso de metástase, segundo dados entre 2009 e 2015 da American Cancer Society. Neste sentido, é de suma importância identificar biomarcadores em dados genômicos para ajudar a prever o avanço do carcinoma renal de células claras (ccRCC), sendo este o subtipo mais frequente. Assim, realizamos um estudo com o objetivo de avaliar assinaturas gênicas e propor uma nova assinatura com maior poder preditivo. Usando coortes ccRCC do The Cancer Genome Atlas (TCGA-KIRC) e do International Cancer Genome Consortium (ICGC-RECA), avaliamos modelos de sobrevida usando regressão de Cox comparando 14 assinaturas da literatura e seis métodos de seleção de características, e também realizamos análise funcional e de expressão diferencial. Neste estudo, apresentamos uma assinatura de 13 genes (AR, AL353637.1, DPP6, FOXJ1, GNB3, HHLA2, IL4, LIMCH1, LINC01732, OTX1, SAA1, SEMA3G, ZIC2) cujos níveis de expressão são capazes de prever risco de pacientes com ccCRC. A assinatura genética de melhor desempenho foi alcançada usando o método de comitês de Mínima Redundância e Máxima Relevância (mRMR). Essa assinatura apresenta características únicas em relação às demais, como a generalização por diferentes coortes e o enriquecimento funcional em vias relacionadas à doenças: Doença Renal Crônica, Carcinoma de células de transição, e Nefrolitíase. Dos 13 genes em nossa assinatura, oito são conhecidos na literatura por estarem correlacionados com a sobrevida de pacientes com ccRCC. Nosso modelo mostrou um desempenho de 0,82 usando a métrica Receiver Operator Characteristic (ROC) Area Under Curve (AUC). Nossos resultados revelaram dois agrupamentos de genes com alta expressão (SAA1, OTX1, ZIC2, LINC01732, GNB3 e IL4) e baixa expressão (AL353637.1, AR, HHLA2, LIMCH1, SEMA3G, e DPP6), ambos correlacionados com prognóstico desfavoráveis. Esta assinatura pode potencialmente ser desenvolvida para auxiliar tratamentos na prática clínica.Artigo Pharmacogenomic Profile of Amazonian Amerindians(MDPI AG, 2022-06-10) Rodrigues, Juliana Carla Gomes; Fernandes, Marianne Rodrigues; Ribeiro-dos-Santos, André Maurício; Araújo, Gilderlanio Santana de; Souza, Sandro José de; Guerreiro, João Farias; Ribeiro-dos-Santos, Ândrea; Assumpção, Paulo Pimentel de; Santos, Ney Pereira Carneiro dos; Santos, SidneyGiven 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 populationArtigo The genomic profile associated with risk of severe forms of COVID-19 in amazonian native american populations(MDPI, 2022-04-01) Astana, Lucas Favacho; Silva, Thays Amâncio; Gellen, Laura Patrícia Albarello; Vieira, Giovana Miranda; Assunção, Letícia Almeida de; Leitão, Luciana Pereira Colares; Silva, Natasha Monte da; Coelho, Rita de Cássia Calderaro; Alcântara, Angélica Leite de; Vinagre, Lui Wallacy Morikawa Souza; Rodrigues, Juliana Carla Gomes; Leal, Diana Feio da Veiga Borges; Fernandes, Marianne Rodrigues Fernandes; Souza, Sandro José de; Kroll, José Eduardo; Santos, André Mauricio Riberio dos; Burbano, Rommel Mario Rodríguez Burbano; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Santos, Ândrea Campos Ribeiro dos; Santos, Sidney Emanuel Batista dos; Santos, Ney Pereira Carneiro dos.Genetic factors associated with COVID-19 disease outcomes are poorly understood. This study aimed to associate genetic variants in the SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, and ABO genes with the risk of severe forms of COVID-19 in Amazonian Native Americans, and to compare the frequencies with continental populations. The study population was composed of 64 Amerindians from the Amazon region of northern Brazil. The difference in frequencies between the populations was analyzed using Fisher’s exact test, and the results were significant when p ≤ 0.05. We investigated 64 polymorphisms in 7 genes; we studied 47 genetic variants that were new or had impact predictions of high, moderate, or modifier. We identified 15 polymorphisms with moderate impact prediction in 4 genes (ABO, CXCR6, FYCO1, and SLC6A20). Among the variants analyzed, 18 showed significant differences in allele frequency in the NAM population when compared to others. We reported two new genetic variants with modifier impact in the Amazonian population that could be studied to validate the possible associations with COVID-19 outcomes. The genomic profile of Amazonian Native Americans may be associated with protection from severe forms of COVID-19. This work provides genomic data that may help forthcoming studies to improve COVID-19 outcomes