Maria Paula Duarte Faustino Goncalves

@min-saude.pt

Departamento de Genética Humana
Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal

Maria Paula Duarte Faustino Goncalves


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https://researchid.co/paulafaustino

RESEARCH INTERESTS

Human Genetics, Rare Diseases, Hemoglobinopathies, Hereditary Hemochromatosis
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Scopus Publications

Scopus Publications

  • Genetic variants in red blood cell adhesion-related genes influence the severity of sickle cell anemia in a malaria-endemic region: Short title: Genetic variants in red blood cell adhesion-related genes in sickle cell anemia
    Irina Matos, Brígida Santos, Elisângela Gonçalves, Pedro Lopes, Miguel Brito, et al.
    Molecular Biology Reports, 2026
    Background Sickle cell anemia (SCA) is a genetic disease marked by abnormal hemoglobin S and sickle-shaped red blood cells. It is highly prevalent in sub-Saharan Africa, especially in Angola, where SCA and malaria are major causes of childhood mortality. This study aimed to explore whether genetic variants in genes associated with red blood cell adhesion to the vascular endothelium influence the manifestations of SCA in Angolan pediatric patients in the context of malaria. Methods and results The study enrolled 65 pediatric SCA patients living in Luanda or Caxito. Their clinical, hematological, and biochemical profiles were monitored through longitudinal pediatric follow-up appointments. Fifteen polymorphic sites were genotyped in CD36 and ICAM-1 genes using PCR, Sanger sequencing, and fragment analysis by capillary electrophoresis. Malaria infection was evaluated by detecting Plasmodium species DNA through PCR analysis of blood spot samples. The CD36 variant rs3211891_C is revealed for the first time as a potential modulator of anemia severity in SCA. Additionally, the CD36 variant rs3211938_G, along with the ICAM-1 variants rs5491_T and rs5496_A, significantly impacted the severity of the hematological phenotype in SCA. Furthermore, SCA patients carrying the ICAM-1 rs5494_T variant showed a 5.63-fold increased risk of having malaria infection compared to those with the wild-type genotype. Conclusions This study enhances our understanding of genetic modifiers of red blood cell adhesion to the vascular endothelium and their influence on the severity of pediatric SCA in the context of frequent concomitant malaria infection in Angola.
  • The Genetics of Iron Metabolism on Biochemical and Hematological Phenotypes of Heart Failure
    Mário Barbosa, Laura Aguiar, Ana Matias, Joana Ferreira, João Caldeira, et al.
    International Journal of Molecular Sciences, 2026
    Heart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791) were evaluated. Variants in HFE and SLC40A1 were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the TMPRSS6 variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure.
  • Hepatitis C Virus: An Overview of Its Chronic Impact on Liver Function, Metabolic Dysregulation, Inflammatory–Oxidative Pathogenesis and Epigenetic Memory
    Joana Ferreira, João Caldeira, Manuel Bicho, Paula Faustino, Fátima Serejo
    International Journal of Molecular Sciences, 2026
    Hepatitis C virus (HCV) infection is a global health concern, chronically affecting over 71 million people. It primarily targets the liver but also causes systemic complications through inflammation, oxidative stress, and metabolic dysregulation. HCV is a highly variable RNA virus with six major genotypes that are mainly transmitted via blood. Often asymptomatic, the infection progresses silently to chronic hepatitis C (CHC), which can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Direct-acting antivirals (DAAs) have revolutionized treatment, achieving cure rates above 95%, improving liver function, reversing fibrosis, and normalizing metabolism. HCV disrupts iron metabolism by suppressing hepcidin, causing iron overload and oxidative stress. It also alters lipid metabolism, inducing steatosis, and affects glucose metabolism, contributing to insulin resistance and type 2 diabetes. DAAs improve these metabolic outcomes. HCV promotes oxidative stress via viral proteins, damaging liver cells and DNA and triggering inflammation and fibrogenesis. Even post-cure, oxidative stress and iron overload may continue to drive disease progression. Genetic and epigenetic factors influence fibrosis progression and HCC risk. Despite a sustained virologic response (SVR), patients with advanced liver damage remain at risk for HCC and metabolic diseases, highlighting the need for continued monitoring and personalized post-treatment care.
  • Iron Metabolism Genes Shape the Course of Liver Fibrosis in Chronic Hepatitis C: From Disease Progression to Reversal After Direct-Acting Antivirals Treatment
    Joana Ferreira, Manuel Bicho, Paula Faustino, Fátima Serejo
    Viruses, 2025
    Chronic hepatitis C (CHC) is linked to iron overload, which significantly correlates with liver fibrosis. This study aimed to assess whether genetic polymorphisms related to iron metabolism are associated with fibrosis severity, predict improvement in fibrosis after HCV clearance with direct-acting antivirals (DAAs) and influence iron-related metabolic markers before treatment. A total of 329 CHC patients were included, 134 of whom received DAAs therapy. Liver fibrosis was assessed using transient elastography (FibroScan), and biochemical parameters were measured using standard methods. Eighteen genetic polymorphisms within five iron metabolism-related genes were analyzed using PCR-RFLP, endpoint genotyping, or next-generation sequencing (NGS). Before DAA treatment, patients with severe fibrosis showed higher levels of serum iron (Fe), total iron-binding capacity (TIBC), and ferritin (Ft). SLC40A1 rs1439816_GG was associated with an increased risk of severe fibrosis compared with GC or CC genotypes. SLC40A1 rs11568351_GC genotype was linked to a higher likelihood of remaining cirrhotic after HCV clearance. Elevated iron parameters were observed in carriers HFE C282Y_CY, TF IVS 11 G>A, and BMP2 570 A>T. Overall, polymorphisms in iron metabolism genes may influence both the severity of liver fibrosis prior to treatment, its regression after DAA therapy and the regulation of iron metabolism in CHC patients.
  • Ancestry of the major long-range regulatory site of the α-globin genes in the Portuguese population with the common 3.7 kb α-thalassemia deletion
    Rita Pena, Pedro Lopes, Gisela Gaspar, Armandina Miranda, Paula Faustino
    Molecular Biology Reports, 2024
    Background The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients’ hematological phenotype. Methods and results We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population. Conclusion This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene.
  • Characterization of a cohort of Angolan children with sickle cell anemia treated with hydroxyurea
    Brígida Santos, Catarina Ginete, Elisângela Gonçalves, Mariana Delgadinho, Armandina Miranda, et al.
    Blood Cells Molecules and Diseases, 2024
  • From Stress to Sick(le) and Back Again–Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia
    Marisa Silva, Paula Faustino
    Antioxidants, 2023
    Sickle cell anemia (SCA) is a genetic disease caused by the homozygosity of the HBB:c.20A>T mutation, which results in the production of hemoglobin S (HbS). In hypoxic conditions, HbS suffers autoxidation and polymerizes inside red blood cells, altering their morphology into a sickle shape, with increased rigidity and fragility. This triggers complex pathophysiological mechanisms, including inflammation, cell adhesion, oxidative stress, and vaso-occlusion, along with metabolic alterations and endocrine complications. SCA is phenotypically heterogeneous due to the modulation of both environmental and genetic factors. Pediatric cerebrovascular disease (CVD), namely ischemic stroke and silent cerebral infarctions, is one of the most impactful manifestations. In this review, we highlight the role of oxidative stress in the pathophysiology of pediatric CVD. Since oxidative stress is an interdependent mechanism in vasculopathy, occurring alongside (or as result of) endothelial dysfunction, cell adhesion, inflammation, chronic hemolysis, ischemia-reperfusion injury, and vaso-occlusion, a brief overview of the main mechanisms involved is included. Moreover, the genetic modulation of CVD in SCA is discussed. The knowledge of the intricate network of altered mechanisms in SCA, and how it is affected by different genetic factors, is fundamental for the identification of potential therapeutic targets, drug development, and patient-specific treatment alternatives.
  • Prevalence Rate of Thalassemia Carriers among Individuals with Microcytosis or Hypochromia in Portugal
    Daniela Santos, Marta Barreto, Irina Kislaya, Joana Mendonça, Miguel P. Machado, et al.
    Acta Medica Portuguesa, 2023
    Introduction: Microcytosis and hypochromia result from deficient hemoglobin synthesis in red blood cells and are easily detected in a complete blood count test. These conditions are mainly due to iron nutritional deficiency, but may also result from some genetic diseases, such as thalassemia. The aim of this study was to determine the contribution of β- and α-thalassemia to these abnormal hematological phenotypes in a representative sample of adult individuals living in Portugal who participated in the first Portuguese National Health Examination Survey (INSEF).Methods: Among the 4808 INSEF participants, 204 had microcytosis, hypochromia or both. The corresponding 204 DNAs were screened for changes in the β-globin gene by next-generation sequencing and Sanger sequencing. In addition, α-thalassemia deletions within the α-globin cluster were investigated by Gap-PCR and multiplex ligation-dependent probe amplification.Results: In this selected subgroup of INSEF participants, 54 had α-thalassemia (26%), predominantly caused by the -α3.7kb deletion, and 22 were β-thalassemia carriers (11%) mainly due to point mutations in the β-globin gene previously known in Portugal.Conclusion: Thalassemia trait is a frequent cause of microcytosis or hypochromia in Portugal since this genetic condition was found in 37% of the investigated cases.
  • Genetic modulation of anemia severity, hemolysis level, and hospitalization rate in Angolan children with Sickle Cell Anemia
    Isabel Germano, Brígida Santos, Mariana Delgadinho, Catarina Ginete, Pedro Lopes, et al.
    Molecular Biology Reports, 2022
  • Prevalence of anemia in the Portuguese adult population: results from the first National Health Examination Survey (INSEF 2015)
    C. Samões, I. Kislaya, M. Sousa-Uva, V. Gaio, P. Faustino, et al.
    Journal of Public Health Germany, 2022
    Anemia is a global public health problem with relevant adverse health, social and economic consequences. The objective of this study was to analyze the distribution of the prevalence of anemia in the Portuguese population. This is a cross-sectional population-based study, based on the first Portuguese National Health Examination Survey (INSEF), which included 4812 participants aged 25 to 74 years, with data on hemoglobin levels and self-reported diagnosis of anemia. The socioeconomic status of participants was assessed by education level, employment status and material deprivation. The association between socioeconomic factors and anemia was estimated by adjusted prevalence ratios. The prevalence of anemia overall was 5.8%, 3.1% in men and 8.4% in women. The overall prevalence of moderate–severe anemia was 1.1%. Previously undiagnosed cases represented 92.5%. In men, anemia was associated with age, education, occupation and material deprivation, and in women, with age group and urban typology. Anemia represents a relevant public health issue in Portugal. In women, it is more prevalent among those of childbearing age and older, and in men among older individuals of low socioeconomic status. This information is relevant for developing targeted strategies aimed at the prevention, diagnosis and treatment of anemia.
  • VCAM1, HMOX1 and NOS3 differential endothelial expression may impact sickle cell anemia vasculopathy
    Marisa Silva, Andreia Coelho, Sofia Vargas, Paula Faustino
    Blood Cells Molecules and Diseases, 2022
  • Comparative Evaluation of Classification Indexes and Outlier Detection of Microcytic Anaemias in a Portuguese Sample
    Beatriz N. Leitão, Paula Faustino, Susana Vinga
    Lecture Notes in Computer Science Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics, 2022
  • Interplay between glycemia and the genetics of eNOS and ACE for the susceptibility to the onset and development of hypertension on the Portuguese population
    Laura Aguiar, Joana Ferreira, Andreia Matos, Mário Rui Mascarenhas, Luiz Menezes Falcão, et al.
    Gene Reports, 2021
  • Differences in the genotype frequencies of genes related to blood pressure regulation-a comparative study between South-West Europe and Peri-equatorial Africa
    Laura Aguiar, Ildegário Semente, Joana Ferreira, Andreia Carvalho, Alda P Silva, et al.
    African Health Sciences, 2021
  • Co-Inheritance of alpha-thalassemia and sickle cell disease in a cohort of Angolan pediatric patients
    Brígida Santos, Mariana Delgadinho, Joana Ferreira, Isabel Germano, Armandina Miranda, et al.
    Molecular Biology Reports, 2020
  • Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia
    Marisa Silva, Sofia Vargas, Andreia Coelho, Emanuel Ferreira, Joana Mendonça, et al.
    Blood Cells Molecules and Diseases, 2020
  • Genetic modulators of fetal hemoglobin expression and ischemic stroke occurrence in African descendant children with sickle cell anemia
    Marta Nicolau, Sofia Vargas, Marisa Silva, Andreia Coelho, Emanuel Ferreira, et al.
    Annals of Hematology, 2019
  • Interaction between HFE and haptoglobin polymorphisms and its relation with plasma glutathione levels in obese children
    Laura Aguiar, Cláudia Marinho, Rute Martins, Irina Alho, Joana Ferreira, et al.
    Cellular and Molecular Biology, 2019
  • Population genetics of IFITM3 in Portugal and Central Africa reveals a potential modifier of influenza severity
    Susana David, Vanessa Correia, Liliana Antunes, Ricardo Faria, José Ferrão, et al.
    Immunogenetics, 2018
  • Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-Thalassemia
    Sachith Mettananda, Chris A. Fisher, Deborah Hay, Mohsin Badat, Lynn Quek, et al.
    Nature Communications, 2017
  • Widening the spectrum of deletions and molecular mechanisms underlying alpha-thalassemia
    José Ferrão, Marisa Silva, Lúcia Gonçalves, Susana Gomes, Pedro Loureiro, et al.
    Annals of Hematology, 2017
  • Iron refractory iron deficiency anemia in dizygotic twins due to a novel TMPRSS6 gene mutation in addition to polymorphisms associated with high susceptibility to develop ferropenic anemia
    Joana Pinto, Gustavo Nobre de Jesus, Mónica Palma Anselmo, Lúcia Gonçalves, Daniela Brás, et al.
    Journal of Investigative Medicine High Impact Case Reports, 2017
  • HFE Variants and the Expression of Iron-Related Proteins in Breast Cancer-Associated Lymphocytes and Macrophages
    Oriana Marques, Ana Rosa, Luciana Leite, Paula Faustino, Alexandra Rêma, et al.
    Cancer Microenvironment, 2016
  • Next-generation sequencing of hereditary hemochromatosis-related genes: Novel likely pathogenic variants found in the Portuguese population
    Ricardo Faria, Bruno Silva, Catarina Silva, Pedro Loureiro, Ana Queiroz, et al.
    Blood Cells Molecules and Diseases, 2016
  • Hemorheological alterations in sickle cell anemia and their clinical consequences - The role of genetic modulators
    Marisa Silva, Sofia Vargas, Andreia Coelho, Alexandra Dias, Teresa Ferreira, et al.
    Clinical Hemorheology and Microcirculation, 2016