Ecocardiografia de pacientes talassêmicos sem insuficiência cardíaca em tratamento com transfusões sanguíneas e quelação

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Hemoglobin and HFE gene polymorphisms in Brazilian populations in regions endemic for malaria

Our objective was to determine how the distribution of red blood cell diseases is related to malaria occurrence in north Brazil, a region endemic for malaria. We evaluated the incidence of two mutations in the HFE gene, H63D and C282Y, in two study groups: a control blood donor group, with no indication of malaria infection, and a group constituted of malaria patients of four states of the Amazonian region. The hemoglobin polymorphisms were obtained by HPLC and classical laboratory methodologies, and the two mutations in the HFE gene were assayed by PCR-RFLP. We found a high frequency of alpha thalassemia, but there were no significant differences between blood donors and malaria patients. There were also no significant differences in the frequencies of HbA(2); however, the frequency of HbF was significantly different in individuals with malaria from Para and Rondonia. The mean number of reticulocytes was significantly reduced in the blood donors from the northern region, suggesting an adaptive strategy of these populations to parasitic attack by Plasmodium. Most individuals were heterozygous for the H63D allele of the HFE gene in both study groups. In the blood donors group, the greatest frequency of the H63D allele was found in Caucasians of all the states. In the malaria patients group in Rondonia, there was a high frequency of the H63D allele among the non-Caucasians. In the other states, and in the malaria patients group, the H63D allele was the most frequent among the Caucasians. Based on our results, we suggest that the maintenance of polymorphism of the mutations in the gene HFE can be explained by selective factors other than malaria, or it is due to simple allelic oscillation and by the constant gene flow among the populations in Brazil.

Comparison of oxidative stress and the frequency of polymorphisms in the HFE gene between hemoglobin S trait blood donors and sickle cell disease patients

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

HFE gene mutations in Brazilian thalassemic patients

Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron intake and progressive storage and is related to mutations in the HFE gene. Interactions between thalassemia and hemochromatosis may further increase iron overload. The ethnic background of the Brazilian population is heterogeneous and studies analyzing the simultaneous presence of HFE and thalassemia-related mutations have not been carried out. The aim of this study was to evaluate the prevalence of the H63D, S65C and C282Y mutations in the HFE gene among 102 individuals with alpha-thalassemia and 168 beta-thalassemia heterozygotes and to compare them with 173 control individuals without hemoglobinopathies. The allelic frequencies found in these three groups were 0.98, 2.38, and 0.29% for the C282Y mutation, 13.72, 13.70, and 9.54% for the H63D mutation, and 0, 0.60, and 0.87% for the S65C mutation, respectively. The chi-square test for multiple independent individuals indicated a significant difference among groups for the C282Y mutation, which was shown to be significant between the beta-thalassemia heterozygote and the control group by the Fisher exact test (P value = 0.009). The higher frequency of inheritance of the C282Y mutation in the HFE gene among beta-thalassemic patients may contribute to worsen the clinical picture of these individuals. In view of the characteristics of the Brazilian population, the present results emphasize the need to screen for HFE mutations in beta-thalassemia carriers.

Frequency of the HFE C282Y and H63D polymorphisms in Brazilian malaria patients and blood donors from the Amazon region

Malaria is an endemic parasitosis and its causitive agent, Plasmodium, has a metabolism linked to iron supply. HFE is a gene with the polymorphisms C282Y and H63D, which are associated with a progressive iron accumulation in the organism leading to a disease called hereditary hemochromatosis. The aim of the present study was to determine the allelic and genotypic frequencies of the HFE gene polymorphisms in malaria patients and blood donors from the Brazilian Amazon region. We screened 400 blood donors and 400 malaria patients for the HFE C282Y and H63D polymorphisms from four states of the Brazilian Amazon region by polymerase chain reaction and restriction fragment length polymorphism analysis. We did not find any C282Y homozygous individuals, and the only five heterozygous individuals detected were from Pará State. The most frequent genotype in the North region of Brazil was the H63D heterozygote, in both study groups. Our results contribute to the concept that the Brazilian Amazon region should not be regarded as a single entity in South America. These polymorphisms did not influence the symptoms of malaria in the population studied, as neither severe signs nor high parasitemia were observed. Therefore, different hereditary hemochromatosis diagnostic and control measures must be developed and applied within its diverse locations. Investigations are currently being carried out in our laboratory in order to determine the importance of the coexistence of hereditary hemochromatosis in patients affected by parasitic diseases, such as malaria. ©FUNPEC-RP.

Serum ferritin and transferrin saturation levels in β0 and β + thalassemia patients

There have been few studies on the mutations that cause heterozygous beta-thalassemia and how they affect the iron profile. One hundred and thirty-eight individuals were analyzed, 90 thalasemic β0 and 48 thalasemic β+, identified by classical and molecular methods. Mutations in the hemochromatosis (HFE) gene, detected using PCR-RFLP, were found in 30.4% of these beta-thalassemic patients; heterozygosity for H63D (20.3%) was the most frequent. Ferritin levels and transferrin saturation were similar in beta-thalassemics with and without mutations in the HFE gene. Ferritin concentrations were significantly higher in men and in individuals over 40 years of age. Transferrin saturation also was significantly higher in men, but only in those without HFE gene mutations. There was no significant difference in the iron profile among the β0 and β+ thalassemics, with and without HFE gene mutations. The frequency of ferritin values above 200 ng/mL in women and 300 ng/mL in men was also similar in β0 and β+ thalassemics (P > 0.72). Our conclusion is that ferritin levels are variable in the beta-thalassemia, trait regardless of the type of beta-globin mutation. Furthermore, HFE gene polymorphisms do not change the iron profile in these individuals. ©FUNPEC-RP www.funpecrp.com.br.

Frequência dos mutantes C282Y e H63D do gene HFE e sua influência no metabolismo do ferro e na expressão da beta talassemia heterozigota

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da expressão da talassemia Beta no Brasil pela coherança com defeitos de hemocromatose

Pós-graduação em Genética - IBILCE

Estudo Doppler-ecocardiográfico de pacientes com talassemia major em regime de hipertransfusão sanguínea

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Processo oxidativo em doadores de sangue portadores de hemoglobina S e mutantes no gene HFE

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Lipid peroxidation: the role or Ca2+ and protection by calcinine

When calcinine (A-23187) (2 mu M), a known Ca2+ ionophore, is present, a significant protection is observed to a mitochondrial suspension undergoing lipid peroxidation by Fe2+-citrate complex. A-23187 can remove Ca2+, which seems to have an important role in the lipid peroxidation process, from its 'lesive sites' and consequently preventing the damage. This information has importance in terms of knowing the mechanisms and avoiding the damages of lipid peroxidation that occur in some pathological cases such as tumor promotion and hemochromatosis.