Browsing by Author "Germano, Isabel"
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- Co-inheritance of alpha-thalassemia and sickle cell disease in a cohort of Angolan pediatric patientsPublication . Santos, Brígida; Delgadinho, Mariana; Ferreira, Joana; Germano, Isabel; Miranda, Armandina; Arez, Ana Paula; Faustino, Paula; Brito, MiguelThe aim of this study was to explore the association between alpha-thalassemia, fetal hemoglobin, hematological indices, and clinical adverse events in Angolan sickle cell disease pediatric patients. A total of 200 sickle cell disease (SCD) children were sampled in Luanda and Caxito. A venous blood sample was collected and used for hematological analyses, fetal hemoglobin quantification, and genotyping of 3.7 kb alpha-thalassemia deletion by GAP-PCR. The frequency of the 3.7 kb alpha-thalassemia deletion in homozygosity was 12.5% and in heterozygosity was 55.0%. An increase in alpha-thalassemia frequency was observed in children older than 5 years old (11.7% vs. 13.00%). Furthermore, 3.7 kb alpha-thalassemia deletion homozygotes had a significantly higher age of the first manifestation, lower number of blood transfusions by year, higher hemoglobin, lower mean corpuscular volume, mean corpuscular hemoglobin, and lower hemolytic rate observed by a lower number of reticulocytes count. There were no differences in fetal hemoglobin between the three genotypes. Moreover, the number of stroke events, osteomyelitis, splenomegaly, splenectomy, and hepatomegaly were lower when alpha-thalassemia was co-inherited. For the first time in the Angolan population, the effect of alpha-thalassemia deletion in sickle cell disease was analyzed and results reinforce that this trait influences the hematological and clinical aspects and produces a milder phenotype.
- Genetic modulation of anemia severity, hemolysis level, and hospitalization rate in Angolan children with sickle cell anemiaPublication . Germano, Isabel; Santos, Brígida; Delgadinho, Mariana; Ginete, Catarina; Lopes, Pedro; Arez, Ana Paula; Brito, Miguel; Faustino, PaulaBackground: Sickle Cell Anemia (SCA) is a genetic disease caused by the c.20 A > T mutation in the HBB gene, generally characterized by sickle erythrocytes, chronic hemolytic anemia, and vaso-occlusive events. This study aimed to investigate genetic modulators of anemia severity, chronic hemolytic rate, and clinical manifestations in pediatric SCA patients from Angola, where the disease is a severe public health problem. Methods and Results: The study was conducted on 200 SCA children living in Luanda or Caxito province. Their clinical phenotype was collected from patients' hospital records. Hematological and biochemical phenotypes were characterized in steady-state conditions. Twelve polymorphic regions in VCAM1, CD36, and NOS3 genes were genotyped using PCR, RFLP, and Sanger sequencing. CD36 gene promoter variants showed a significant impact on anemia severity. Particularly, the rs1413661_C allele was associated with lower hemoglobin levels and an increased number of hospitalizations and transfusions. This is the first report associating this SNP with SCA phenotypic heterogeneity. Moreover, the rs1041163_C allele in VCAM1 was associated with lower LDH levels; inversely the rs2070744_C allele in NOS3 was related to higher LDH levels and a number of hospitalizations, being a risk factor for increased hemolytic rate. Conclusion: This study highlights, for the first time in the Angolan population, the importance of the genetic modifiers of vascular cell adhesion and nitric oxide metabolism in SCA pediatric phenotypic variability.
- Genetic modulators of hemolytic anemia in Angolan children with sickle cell anemiaPublication . Germano, Isabel; Santos, Brígida; Delgadinho, Mariana; Lopes, Pedro; Arez, Ana Paula; Brito, Miguel; Faustino, PaulaSickle Cell Anemia (SCA) is a recessive genetic disease caused by the c.20A>T variant in the HBB gene. It is characterized by sickled erythrocytes, chronic hemolytic anemia, and vaso-occlusive events. However, these manifestations are heterogeneous due to environmental and genetic modifying factors. The aim of this study was to investigate genetic modifiers of hemolytic anemia in pediatric SCA patients living in Africa, where the disease is a severe public health problem. The study was conducted on 200 Angolan SCA 3-12-year-old children. Thirteen polymorphic regions in genes previously associated with vascular cell adhesion (VCAM1 and CD36), vascular tonus (NOS3), or erythrocyte hemoglobinisation (HBA), were genotyped using PCR, RFLP, Gap-PCR, and Sanger sequencing. Hematological and biochemical phenotypes were obtained at a steady state and clinical adverse events were collected from the patient's medical records. Results revealed a high level (67.5%) of α-thalassemia co-inheritance (del. 3.7kb in HBA), which improves patients’ health by delaying the onset of the disease, decreasing anemia, and the number of blood transfusions. Two SNPs in CD36 (rs1984112 and rs1413661) showed an impact on anemia severity. Particularly, genotypes containing the rs1413661_allele C were revealed to be risk factors for severe anemia, as they were associated with lower hemoglobin levels, increased number of hospitalizations, and transfusions. This is the first report associating this SNP with SCA pathology. Moreover, the rs1041163_allele C in VCAM1 was associated with lower LDH levels, inversely the rs2070744_allele C in NOS3 was associated with higher LDH levels and a higher number of hospitalizations, being a possible risk factor for increased hemolytic rate. This study contributed to the understanding of SCA complex pathophysiology. It confirmed the positive role of α-thal., both in SCA-related anemia and in its clinical manifestations. In addition, it reinforced the importance of vascular cell adhesion in hemolytic anemia variability. In this context, we propose the SNP rs1413661 in CD36 as an important novel genetic modulator of SCA in Africa.