Butyrylcholinesterase as a potential biomarker of metabolic imbalances in Afro-descendant populations Denise Raquel de Moura Bones, Marcia Machado Ramos, Natali Fátima Veigand, Iriel Araceli Joerin-Luque, Natalie Mary Sukow, et al. International Journal of Obesity, 2026 Background This study investigated butyrylcholinesterase (BChE) activity and its genetic variants (−116, A, and K) in Afro-Brazilian individuals living in two African-derived communities (quilombos) in southern Brazil. Parameters, including obesity, glucose, and lipid profile, were compared with those of Euro-Brazilian individuals from the same region. The study aimed to characterize population parameters and assess their influence on factors involved in metabolic syndrome, obesity, and type 2 diabetes mellitus (TDM2). Methods A total of 198 Afro-Brazilians and 114 Euro-Brazilians participated. BChE activity was measured using the Ellman method, and variants were genotyped by PCR-SSP. Statistical analyses included t -test or Mann–Whitney, ANOVA, chi-square or Fisher’s exact test, correlations, and age- and sex-adjusted regression models. Results The mean BChE activity in the Quilombola population was 3.71 U/mL and was significantly higher in people with TDM2 and/or obesity ( p = 0.016), and associated with triglycerides, total cholesterol, overweight, and male sex. A significant interaction between triglycerides and glycated hemoglobin was observed ( p = 0.016). BChE activity was higher in Quilombolas than in Euro-Brazilians, regardless of metabolic status, suggesting ethnic influence. BCHE gene variants (A, −116, and K) showed frequencies similar to other populations. Although enzymatic activity varied among haplotypes, differences were not statistically significant. These results highlight the relevance of clinical and ethnic factors in interpreting BChE activity. Conclusions This study revealed higher BChE activity and TDM2 prevalence in Afro-Brazilian populations compared to Euro-Brazilians, and these differences correlate with non-genetic factors. The BCHE genetic variants investigated showed no robust associations after correction for multiple testing, suggesting that their effects on metabolic traits may be subtle and context-dependent. This is the first study to quantify BChE activity in Afro-Brazilian Quilombola populations and the second in Black individuals in Brazil, highlighting the importance of considering genetic and ethnic factors in metabolic risk assessment.
Tracing the Uncharted African Diaspora in Southern Brazil: The Genetic Legacies of Resistance in Two Quilombos from Paraná Iriel A. Joerin-Luque, Isadora Baldon Blaczyk, Priscila Ianzen dos Santos, Ana Cecília Guimarães Alves, Natalie Mary Sukow, et al. Genes, 2025 Background/Objectives: In Brazil, quilombos—African-descendant resistance communities—emerged during slavery and persisted beyond its abolition. The state of Paraná, in Southern Brazil, is home to 86 quilombos, yet their genetic diversity remains entirely unexplored, and little is known about their subcontinental African origins. Methods: To explore the demographic history of these communities and the reach of the Transatlantic Slave Trade in Southern Brazil, we analyzed Y and mitochondrial DNA haplotypes in samples from two quilombo communities from Paraná, Feixo (n = 117) and Restinga (n = 47). Results: Our findings reveal a significant African maternal ancestry in both communities, with Feixo exhibiting 35% and Restinga showing a striking 78.72% of maternal haplogroups of African origin. Feixo’s mtDNA haplotypes display affinities with Bantu-speaking populations from Central-Western and Southeastern Africa (such as Angola, Congo, and Mozambique), whereas those found in Restinga are more closely aligned with lineages frequent in Western Africa. Y-chromosome data reveal 39.4% and 25% African paternal ancestry in Feixo and Restinga, respectively, with most African chromosomes assigned to haplogroup E1b1b1-M35, which has a broad frequency across eastern Africa. Conclusions: These results offer novel insights into the history of the African diaspora in a previously unstudied Brazilian region, suggesting African sources—including underdocumented Eastern/Southern lineages—and contributing useful new clues to their broader within-Africa affinities.
The Current State of Breast Cancer Genetics in Populations of African Ancestry Sarah Elisabeth Santos Cupertino, Ana Carolina Aparecida Gonçalves, Claudemira Vieira Gusmão Lopes, Daniela Fiori Gradia, Marcia Holsbach Beltrame Genes, 2025 Breast cancer (BC) constitutes a significant global health burden, particularly among women, with disparities observed across populations. Notably, women of African ancestry often experience BC at earlier ages and in more aggressive forms, with a higher prevalence of metastasis. Genetic studies, including those focused on BRCA1 and BRCA2 genes, have revealed population-specific variations in BC susceptibility. Despite efforts to investigate BC genetics in African and African-descendant populations, research remains limited compared to studies conducted in populations of European descent. Socioeconomic factors further compound the challenges faced by marginalized populations, influencing disease outcomes and treatment efficacy. This review explores the BC literature in African and African-descendant populations, highlighting population-specific genetic variants associated with the disease’s subtypes, treatment response, and disease evolution. Limited sample sizes and lack of data on genetic ancestry hinder the development of precise risk stratification and treatment strategies. Efforts to expand research, improve data collection, and enhance genetic analyses in diverse populations are crucial steps toward addressing racial disparities and advancing BC care on a global scale.
LncRNA-SNPs in a Brazilian Breast Cancer Cohort: A Case-Control Study Carolina Mathias, Anelis Maria Marin, Ana Flávia Kohler, Heloisa Bruna Soligo Sanchuki, Natalie Sukow, et al. Genes, 2023 Long noncoding RNAs (lncRNAs) are a class of non-coding RNAs that contain more than 200 nucleotides and exhibit a versatile regulatory capacity. Genomic alterations in lncRNAs have already been investigated in several complex diseases, including breast cancer (BC). BC is a highly heterogeneous disease and is the most prevalent cancer type among women worldwide. Single nucleotide polymorphisms (SNPs) in lncRNA regions appear to have an important role in BC susceptibility; however, little is known about lncRNA-SNPs in the Brazilian population. This study used Brazilian tumor samples to identify lncRNA-SNPs with a biological role in BC development. We applied a bioinformatic approach intersecting lncRNAs that are differentially expressed in BC tumor samples using The Cancer Genome Atlas (TCGA) cohort data and looked for lncRNAs with SNPs associated with BC in the Genome Wide Association Studies (GWAS) catalog. We highlight four lncRNA-SNPs—rs3803662, rs4415084, rs4784227, and rs7716600—which were genotyped in Brazilian BC samples in a case-control study. The SNPs rs4415084 and rs7716600 were associated with BC development at higher risk. These SNPs were also associated with progesterone status and lymph node status, respectively. The rs3803662/rs4784227 haplotype GT was associated with BC risk. These genomic alterations were also evaluated in light of the lncRNA’s secondary structure and gain/loss of miRNA binding sites to better understand its biological functions. We emphasize that our bioinformatics approach could find lncRNA-SNPs with a potential biological role in BC development and that lncRNA-SNPs should be more deeply investigated in a highly heterogeneous disease population.
Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region Luciana de Brito Vargas, Marcia H Beltrame, Brenda Ho, Wesley M Marin, Ravi Dandekar, et al. Molecular Biology and Evolution, 2022 The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR–HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR–HLA interactions among all described worldwide populations, and that 83–97% of their KIR–HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR–HLA coevolution and its impact on human health and survival.
Tracing the Distribution of European Lactase Persistence Genotypes Along the Americas Ana Cecília Guimarães Alves, Natalie Mary Sukow, Gabriel Adelman Cipolla, Marla Mendes, Thiago P. Leal, et al. Frontiers in Genetics, 2021 In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the –13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the –13910C > T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries’ dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of –13910C > T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the –13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the –13910C > T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the –13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.
Ficolin-3 in chronic Chagas disease: Low serum levels associated with the risk of cardiac insufficiency Kárita Cláudia Freitas Lidani, Fabiana Antunes Andrade, Marcia Holsbach Beltrame, Indira Chakravarti, Maria Regina Tizzot, et al. Parasite Immunology, 2021 To investigate whether FCN3 polymorphisms and circulating ficolin‐3 levels were associated with clinical forms of chronic Chagas disease (CD) and to assess their potential use as biomarkers for the disease or its severity.
Butyrylcholinesterase as a potential biomarker of metabolic imbalances in Afro-descendant populations: Epidemiology and Population Health DR de Moura Bones, MM Ramos, NF Veigand, I Araceli Joerin-Luque, ... International Journal of Obesity, 1-10 , 2026 2026
Tracing the Uncharted African Diaspora in Southern Brazil: The Genetic Legacies of Resistance in Two Quilombos from Paraná IA Joerin-Luque, I Baldon Blaczyk, P Ianzen dos Santos, ... Genes 16 (12), 1510 , 2025 2025
The current state of breast cancer genetics in populations of African ancestry SES Cupertino, ACA Gonçalves, CV Gusmão Lopes, DF Gradia, ... Genes 16 (2), 199 , 2025 2025 Citations: 9
O que a (in) tolerância à lactose nos conta sobre a evolução humana? NM Sukow, MH Beltrame Genética na Escola 18 (2), 100-108 , 2023 2023 Citations: 1
LncRNA-SNPs in a Brazilian Breast Cancer Cohort: A Case-Control Study C Mathias, AM Marin, AF Kohler, HBS Sanchuki, N Sukow, MH Beltrame, ... Genes 14 (5), 971 , 2023 2023 Citations: 4
Natural killer cell receptor variation is associated with more aggressive subtypes of breast cancer L Amorim, M Beltrame, E Ribeiro, JA Hollenbach, D Augusto HLA 101 (4), 343-344 , 2023 2023
Whole-genome sequencing reveals a complex African population demographic history and signatures of local adaptation S Fan, JP Spence, Y Feng, MEB Hansen, J Terhorst, MH Beltrame, ... Cell 186 (5), 923-939. e14 , 2023 2023 Citations: 115
Ancestry, diversity, and genetics of health-related traits in African-derived communities ( quilombos ) from Brazil IA Joerin-Luque, NM Sukow, IDO Bucco, JG Tessaro, CVG Lopes, ... Functional & Integrative Genomics 23 (1), 74 , 2023 2023 Citations: 11
Uniparental markers reveal new insights on subcontinental ancestry and sex-biased admixture in Brazil IA Joerin-Luque, DG Augusto, V Calonga-Solís, RC de Almeida, ... Molecular Genetics and Genomics 297 (2), 419-435 , 2022 2022 Citations: 4
Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region L de Brito Vargas, MH Beltrame, B Ho, WM Marin, R Dandekar, ... Molecular biology and evolution 39 (1), msab298 , 2022 2022 Citations: 19
Tracing the distribution of European lactase persistence genotypes along the Americas AC Guimarães Alves, NM Sukow, G Adelman Cipolla, M Mendes, TP Leal, ... Frontiers in genetics 12, 671079 , 2021 2021 Citations: 15
Ficolin‐3 in chronic Chagas disease: Low serum levels associated with the risk of cardiac insufficiency KCF Lidani, FA Andrade, MH Beltrame, I Chakravarti, MR Tizzot, ... Parasite Immunology 43 (6), e12829 , 2021 2021 Citations: 4
MASPs at the crossroad between the complement and the coagulation cascades-the case for COVID-19 V Bumiller-Bini, C de Freitas Oliveira-Toré, TM Carvalho, GC Kretzschmar, ... Genetics and Molecular Biology 44 (1 Suppl 1), e20200199 , 2021 2021 Citations: 39
Single Nucleotide Polymorphism in KIR2DL1 Is Associated With HLA-C Expression in Global Populations LB Vargas, RM Dourado, LM Amorim, B Ho, V Calonga-Solís, HC Issler, ... Frontiers in Immunology 11, 1881 , 2020 2020 Citations: 20
Natural killer cell receptor variants and chronic hepatitis B virus infection in the Vietnamese population ED Auer, H Van Tong, LM Amorim, D Malheiros, NX Hoan, HC Issler, ... International Journal of Infectious Diseases 96, 541-547 , 2020 2020 Citations: 16
Clinical and epidemiological aspects of chronic Chagas disease from Southern Brazil KCF Lidani, TL Sandri, R Castillo-Neyra, FA Andrade, CM Guimarães, ... Revista da Sociedade Brasileira de Medicina Tropical 53, e20200225 , 2020 2020 Citations: 26
Condemned or not to die? Gene polymorphisms associated with cell death in pemphigus foliaceus V Bumiller-Bini, GA Cipolla, MB Spadoni, DG Augusto, ML Petzl-Erler, ... Frontiers in Immunology 10, 2416 , 2019 2019 Citations: 20
Genetic and epigenetic fine mapping of complex trait associated loci in the human liver M Çalışkan, E Manduchi, HS Rao, JA Segert, MH Beltrame, M Trizzino, ... The American Journal of Human Genetics 105 (1), 89-107 , 2019 2019 Citations: 66
Chagas disease: from discovery to a worldwide health problem KC Freitas Lidani, FA Andrade, L Bavia, FS Damasceno, MH Beltrame, ... Frontiers in Public Health 7 , 2019 2019
Chagas disease: from discovery to a worldwide health problem KCF Lidani, FA Andrade, L Bavia, FS Damasceno, MH Beltrame, ... Frontiers in public health 7, 166 , 2019 2019 Citations: 750
MOST CITED SCHOLAR PUBLICATIONS
Chagas disease: from discovery to a worldwide health problem KCF Lidani, FA Andrade, L Bavia, FS Damasceno, MH Beltrame, ... Frontiers in public health 7, 166 , 2019 2019 Citations: 750
Loci associated with skin pigmentation identified in African populations NG Crawford, DE Kelly, MEB Hansen, MH Beltrame, S Fan, SL Bowman, ... Science 358 (6365), eaan8433 , 2017 2017 Citations: 440
African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations S Fan, DE Kelly, MH Beltrame, MEB Hansen, S Mallick, A Ranciaro, ... Genome Biology 20 (1), 82 , 2019 2019 Citations: 189
The lectin pathway of complement and rheumatic heart disease MH Beltrame, SJ Catarino, I Goeldner, ABW Boldt, IJ de Messias-Reason Frontiers in pediatrics 2, 148 , 2015 2015 Citations: 161
Whole-genome sequencing reveals a complex African population demographic history and signatures of local adaptation S Fan, JP Spence, Y Feng, MEB Hansen, J Terhorst, MH Beltrame, ... Cell 186 (5), 923-939. e14 , 2023 2023 Citations: 115
MBL-associated serine proteases (MASPs) and infectious diseases MH Beltrame, ABW Boldt, SJ Catarino, HC Mendes, SE Boschmann, ... Molecular immunology 67 (1), 85-100 , 2015 2015 Citations: 89
Genetic and epigenetic fine mapping of complex trait associated loci in the human liver M Çalışkan, E Manduchi, HS Rao, JA Segert, MH Beltrame, M Trizzino, ... The American Journal of Human Genetics 105 (1), 89-107 , 2019 2019 Citations: 66
Unveiling the Diversity of Immunoglobulin Heavy Constant Gamma ( IGHG ) Gene Segments in Brazilian Populations Reveals 28 Novel Alleles and Evidence of … V Calonga-Solís, D Malheiros, MH Beltrame, LB Vargas, RM Dourado, ... Frontiers in immunology 10, 1161 , 2019 2019 Citations: 52
MASPs at the crossroad between the complement and the coagulation cascades-the case for COVID-19 V Bumiller-Bini, C de Freitas Oliveira-Toré, TM Carvalho, GC Kretzschmar, ... Genetics and Molecular Biology 44 (1 Suppl 1), e20200199 , 2021 2021 Citations: 39
Inferences of African evolutionary history from genomic data MH Beltrame, MA Rubel, SA Tishkoff Current Opinion in Genetics & Development 41, 159-166 , 2016 2016 Citations: 39
Association of MASP2 polymorphisms and protein levels with rheumatic fever and rheumatic heart disease SJ dos Santos Catarino, ABW Boldt, MH Beltrame, RM Nisihara, ... Human Immunology 75 (12), 1197-1202 , 2014 2014 Citations: 36
Association of polymorphisms in HCN4 with mood disorders and obsessive compulsive disorder B Kelmendi, M Holsbach-Beltrame, AM McIntosh, L Hilt, ED George, ... Neuroscience letters 496 (3), 195-199 , 2011 2011 Citations: 33
Polymorphisms in the 2q33 and 3q21 chromosome regions including T-cell coreceptor and ligand genes may influence susceptibility to pemphigus foliaceus R Dalla-Costa, MÂR Pincerati, MÂH Beltrame, D Malheiros, ... Human Immunology 71 (8), 809-817 , 2010 2010 Citations: 32
Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy FA Andrade, MH Beltrame, VB Bini, LB Goncalves, ABW Boldt, ... PLoS neglected tropical diseases 11 (2), e0005409 , 2017 2017 Citations: 30
Clinical and epidemiological aspects of chronic Chagas disease from Southern Brazil KCF Lidani, TL Sandri, R Castillo-Neyra, FA Andrade, CM Guimarães, ... Revista da Sociedade Brasileira de Medicina Tropical 53, e20200225 , 2020 2020 Citations: 26
FRONT PUBLIC HEALTH KCF Lidani, FA Andrade, L Bavia, FS Damasceno, MH Beltrame, ... V7, DOI 10 , 2019 2019 Citations: 21
Single Nucleotide Polymorphism in KIR2DL1 Is Associated With HLA-C Expression in Global Populations LB Vargas, RM Dourado, LM Amorim, B Ho, V Calonga-Solís, HC Issler, ... Frontiers in Immunology 11, 1881 , 2020 2020 Citations: 20
Condemned or not to die? Gene polymorphisms associated with cell death in pemphigus foliaceus V Bumiller-Bini, GA Cipolla, MB Spadoni, DG Augusto, ML Petzl-Erler, ... Frontiers in Immunology 10, 2416 , 2019 2019 Citations: 20
Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region L de Brito Vargas, MH Beltrame, B Ho, WM Marin, R Dandekar, ... Molecular biology and evolution 39 (1), msab298 , 2022 2022 Citations: 19
Differential ability to resist to complement lysis and invade host cells mediated by MBL in R4 and 860 strains of Trypanosoma cruzi I Evans-Osses, A Mojoli, MH Beltrame, DE Da Costa, WD DaRocha, ... FEBS letters 588 (6), 956-961 , 2014 2014 Citations: 19