Abstract Genetic variability in the host metabolism of antimalarial drugs influenced by the polymorphisms of cytochrome P450 (CYP) could lead to significant changes in antimalarial treatment response. However, little is known about the frequency of alleles CYP2B6, CYP2C8, and CYP2D6 in an Amazonian population, especially with vivax malaria. Therefore, this study aimed to determine the frequency of CYP alleles CYP2B6*6, CYP2C8*3, and CYP2D6*4 in patients with vivax malaria. The study included 231 patients with vivax malaria treated at a health care reference in Manaus, northern Brazil. A sample of peripheral blood from each subject was collected to perform DNA extraction and genotypic analysis. Genotyping of polymorphisms was performed by allelic discrimination using Real-time polymerase chain reaction. The CYP2D6*4 allele was the most prevalent among patients who developed severe malaria. The frequencies of the CYP2B6*6 and CYP2D6*4 were not different between the severe and uncomplicated malaria. There was a significant association between heterozygous CYP2D6*4 and severe cases of malaria. The results are in agreement with other reports described in the literature for different populations. Future studies are needed to understand the clinical implications of the polymorphisms in patients with vivax malaria.

Abstract INTRODUCTION: We investigated the prevalence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) infection in patients with hematological diseases from the western Amazon region of Brazil. METHODS: Samples from 306 patients were submitted for the molecular diagnosis of HTLV-1/2 infection by real time PCR (qPCR), with amplification, sequencing, and phylogenetic analysis of the long terminal repeat (LTR) region. RESULTS: A 29-year-old male carrier of sickle cell anemia with a history of multiple blood transfusions was diagnosed with the HTLV-2c subtype. CONCLUSIONS: This study describes the first known occurrence of HTLV-2c in the urban area of Brazil’s western Amazon region.

Abstract: INTRODUCTION: In the Brazilian Amazon, malaria infections are primarily caused by Plasmodium vivax. The only drug that kills the hypnozoite form of P. vivax is primaquine, thereby preventing relapse. However, treating glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals with primaquine can lead to severe hemolysis. G6PD deficiency (G6PDd) affects approximately 400 million people worldwide, most of whom live in malaria-endemic areas. Therefore, clinicians need tools that can easily and reliably identify individuals with G6PDd. This study estimated the accuracy of the Carestart(tm) G6PD rapid test (Access Bio) in the diagnosis of G6PDd in male participants with and without P. vivax acute malaria. METHODS: Male participants were recruited in Manaus. Malaria diagnosis was determined by thick blood smear. G6PD quantitative analysis was performed spectro photometrically at a wave length of 340nm. The Carestart(tm) G6PD test was performed using venous blood. Genotyping was performed for individuals whose samples had an enzyme activity less than 70% of the normal value. RESULTS: Six hundred and seventy-four male participants were included in this study, of whom 320 had a diagnosis of P. vivax malaria. In individuals with enzyme activity lower than 30% (n=13), the sensitivity, specificity, positive predictive value, and negative predictive value of the Carestart(tm) G6PD test were as follows: 61.5% (95%CI: 35.5%-82.3%), 98.3% (95%CI: 97.0%-99.1%), 42.1% (95%CI: 23.1%-63.7%), and 99.2% (95%CI: 98.2%-82.3%), 98.3% (95%CI: 97.0%-99.1%), 42.1% (95%CI: 23.1%-63.7%), and 99.2% (95%CI: 98.2%-99.7%), respectively. Increases in sensitivity were observed when increasing the cut-off value. CONCLUSIONS: Despite low sensitivity, Carestart(tm) G6PD remains a good alternative for rapid diagnosis of G6PDd in malaria-endemic regions.

The null genotype for glutathione S-transferase (GST, EC 2.5.1.18) gene polymorphisms is considered a risk factor for leukemia in different populations. In this work we investigated the GSTT1 and GSTM1 polymorphisms using multiplex PCR in 53 patients with chronic myeloid leukemia (CML), 23 with acute promyelocytic leukemia (APL) and 304 apparently healthy controls. In this association study we found that the GSTT1null genotype was more frequent in our group of APL patients than in the control group [OR = 2.75 (95% CI = 1.10-6.88)], providing evidence that a deletion in the GSTT1 gene could be a risk factor for this type of leukemia.

Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficiency is the most common enzyme deficiency worldwide, causing a spectrum of diseases including neonatal hyperbilirubinemia and acute or chronic hemolysis. We used the methemoglobin reduction test and G6PD electrophoresis to screen 655 neonates (354 females and 301 males) for common G6PD mutations in the city of Salvador in the Northeastern Brazilian state Bahia and found that 66 (10.1%) were G6PD-deficient (41 females and 25 males). The 66 (10.1%) G6PD-deficient neonates were assessed for the c.376 A -> G (exon 5) and c.202 G -> A (exon 4) mutations using the polymerase chain reaction and restriction enzyme fragment length polymorphism (PCR-RFLP) analysis and the results validated by DNA sequencing. Of the 66 G6PD-deficient neonates investigated we found that 54 (81.8%) presented the c.376 A -> G (p.Asn126Asp) and c.202 G -> A (p.Val68Met) mutations, two (3%) had the c.376 A -> G mutation only, two (3%) had the c.202 G -> A mutation only, five (7.6%) exhibited a previously unrecorded 197T -> A (p.Phe66Thr) substitution in exon 4 and three showed no mutations at any of these sites. Of the five neonates exhibiting the new 197T -> A (p.Phe66Thr) substitution, four (6.1%) also presented the c.202 G -> A and c.376 A -> G mutations and one (1.5%) had the c.[197T -> A / 202 G -> A] combination. We propose to name the new variant G6PD Bahia.

Methylenetetrahydrofolate reductase (MTHFR: EC 1.5.1.20) polymorphisms are associated to acute lymphoid leukemia in different populations. We used the polymerase chain reaction and the restriction fragment length polymorphism method (PCR-RFLP) to investigate MTHFR C677T and A1298C polymorphism frequencies in 67 patients with chronic myeloid leukemia (CML), 27 with acute myeloid leukemia FAB subtype M3 (AML-M3) and 100 apparently healthy controls. The MTHFR mutant allele frequencies were as follows: CML = 17.2% for C677T, 21.6% for A1298C; AML-M3 = 22.2% for C677T, 24.1% for A1298C; and controls = 20.5% for C677T, 21% for A1298C. Taken together, our results provide evidence that MTHFR polymorphisms have no influence on the development of CML or AML-M3.

Hemoglobinopatias são alterações hereditárias na molécula de hemoglobina com prevalência mundial elevada. O Brasil apresenta prevalência de 0,1 a 0,3% para recém-nascidos com anemia falciforme e freqüência de 20,0 a 25,0% para a ocorrência de heterozigotos da talassemia alfa2 entre indivíduos afro-descendentes. O presente estudo investigou a presença de hemoglobinas variantes e talassemia alfa2(3.7Kb) e alfa2(4.2Kb) em recém-nascidos de Salvador, Bahia, Brasil. Analisamos o sangue do cordão umbilical de 590 recém-nascidos, sendo 57 (9,8%) com padrão FAS; 36 (6,5%) FAC; um (0,2%) SF e cinco (0,9%) FSC. Cento e catorze (22,2%) apresentaram talassemia alfa2(3.7Kb), dos quais 101 (19,7%) foram heterozigotos e 13 (2,5%) homozigotos, mostrando significância estatística para os dados hematológicos entre recém-nascidos com genes alfa normais e portadores de talassemia alfa2(3.7Kb). A talassemia alfa2(4.2Kb) não foi encontrada. As freqüências descritas neste trabalho confirmam que as hemoglobinopatias são um problema de Saúde Pública no Brasil, enfatizando a importância dos programas de triagem neonatal e aconselhamento genético.

Hemoglobinopathies are hereditary disorders of the hemoglobin molecule with a high prevalence worldwide. Brazil has a prevalence of 0.1 to 0.3% of newborns with sickle cell anemia and 20.0 to 25.0% of heterozygous alpha2 thalassemia among African Brazilians. In the present study, we investigated the presence of variant hemoglobins and alpha2(3.7 Kb) and alpha2(4.2 Kb) thalassemia in newborns from Salvador, Bahia, Brazil. Samples of umbilical cord blood from a total of 590 newborns were analyzed, of which 57 (9.8%) were FAS; 36 (6.5%) FAC; one (0.2%) SF; and five (0.9%) FSC. One hundred fourteen (22.2%) newborns had alpha2(3.7 Kb) thalassemia, of whom 101 (19.7%) were heterozygous and 13 (2.5%) homozygous, showing statistical significance for hematological data between newborns with normal alpha genes and alpha2(3.7 Kb) thalassemia carriers. The alpha2(4.2 Kb) thalassemia was not found. Frequencies found in the present study confirm that hemoglobinopathies are a public health problem in Brazil, emphasizing the need for neonatal screening and genetic counseling programs.

Hemoglobinopatias são alterações hereditárias na molécula de hemoglobina com prevalência mundial elevada. O Brasil apresenta prevalência de 0,1 a 0,3% para recém-nascidos com anemia falciforme e freqüência de 20,0 a 25,0% para a ocorrência de heterozigotos da talassemia alfa2 entre indivíduos afro-descendentes. O presente estudo investigou a presença de hemoglobinas variantes e talassemia alfa2(3.7Kb) e alfa2(4.2Kb) em recém-nascidos de Salvador, Bahia, Brasil. Analisamos o sangue do cordão umbilical de 590 recém-nascidos, sendo 57 (9,8%) com padrão FAS; 36 (6,5%) FAC; um (0,2%) SF e cinco (0,9%) FSC. Cento e catorze (22,2%) apresentaram talassemia alfa2(3.7Kb), dos quais 101 (19,7%) foram heterozigotos e 13 (2,5%) homozigotos, mostrando significância estatística para os dados hematológicos entre recém-nascidos com genes alfa normais e portadores de talassemia alfa2(3.7Kb). A talassemia alfa2(4.2Kb) não foi encontrada. As freqüências descritas neste trabalho confirmam que as hemoglobinopatias são um problema de Saúde Pública no Brasil, enfatizando a importância dos programas de triagem neonatal e aconselhamento genético.

Hemoglobinopathies are hereditary disorders of the hemoglobin molecule with a high prevalence worldwide. Brazil has a prevalence of 0.1 to 0.3% of newborns with sickle cell anemia and 20.0 to 25.0% of heterozygous alpha2 thalassemia among African Brazilians. In the present study, we investigated the presence of variant hemoglobins and alpha2(3.7 Kb) and alpha2(4.2 Kb) thalassemia in newborns from Salvador, Bahia, Brazil. Samples of umbilical cord blood from a total of 590 newborns were analyzed, of which 57 (9.8%) were FAS; 36 (6.5%) FAC; one (0.2%) SF; and five (0.9%) FSC. One hundred fourteen (22.2%) newborns had alpha2(3.7 Kb) thalassemia, of whom 101 (19.7%) were heterozygous and 13 (2.5%) homozygous, showing statistical significance for hematological data between newborns with normal alpha genes and alpha2(3.7 Kb) thalassemia carriers. The alpha2(4.2 Kb) thalassemia was not found. Frequencies found in the present study confirm that hemoglobinopathies are a public health problem in Brazil, emphasizing the need for neonatal screening and genetic counseling programs.

O polimorfismo C677T no gene da MTHFR tem sido associado ao aumento dos níveis séricos de homocisteína.total (tHcy), descrito como fator de risco para o desenvolvimento de doenças cardiovasculares. Oitocentos e quarenta e três recém-nascidos (RNs), de duas maternidades diferentes, uma pública e a outra privada, em Salvador, Bahia, Brasil foram triados para o polimorfismo C677T por PCR e RFLP. A freqüência do alelo T foi de 0,23 e as prevalências dos genótipos C/T e T/T foram de 36,2% e 5,3%, respectivamente. A freqüência do alelo T diferiu e a prevalência do genótipo T/T foi mais elevada entre os RNs da maternidade privada. O perfil de hemoglobinas (Hb) foi determinado por HPLC em 763 RNs. A freqüência de Hbs variantes foi mais elevada entre os RNs da maternidade pública Tsylla Balbino do que na maternidade privada do Hospital Santo Amaro. A associação do polimorfismo C677T e o perfil de Hbs foram estudados em 683 RNs, apresentando freqüência elevada da coexistência do alelo T e Hb variantes. Estes resultados podem ser utilizados como base para estudos futuros sobre riscos potenciais de eventos vaso-oclusivos nestes indivíduos.

The C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) is associated with an increase in total homocysteine serum levels (tHcy), described as a risk factor for cardiovascular disease. Eight hundred forty-three neonates from two different maternity hospitals, one public and another private, in Salvador, Bahia, Brazil were screened for this polymorphism by PCR and RFLP. The T-allele frequency in the total sample was 0.23, and the prevalence rates of heterozygous and homozygous carriers were 36.2% and 5.3%, respectively. The T-allele frequency differed and the T/T genotype was more prevalent at the private maternity hospital. The hemoglobin (Hb) profile was investigated by HPLC in 763 newborns. The frequency of variant Hb was higher at the public than at the private maternity hospital. The association of the C677T polymorphism and the Hb profile was investigated in 683 newborns, showing a relatively high frequency of variant Hbs and the T allele. These data could provide an important basis for further studies focusing on potential risks of vaso-occlusive events in these individuals.

O polimorfismo C677T no gene da MTHFR tem sido associado ao aumento dos níveis séricos de homocisteína.total (tHcy), descrito como fator de risco para o desenvolvimento de doenças cardiovasculares. Oitocentos e quarenta e três recém-nascidos (RNs), de duas maternidades diferentes, uma pública e a outra privada, em Salvador, Bahia, Brasil foram triados para o polimorfismo C677T por PCR e RFLP. A freqüência do alelo T foi de 0,23 e as prevalências dos genótipos C/T e T/T foram de 36,2% e 5,3%, respectivamente. A freqüência do alelo T diferiu e a prevalência do genótipo T/T foi mais elevada entre os RNs da maternidade privada. O perfil de hemoglobinas (Hb) foi determinado por HPLC em 763 RNs. A freqüência de Hbs variantes foi mais elevada entre os RNs da maternidade pública Tsylla Balbino do que na maternidade privada do Hospital Santo Amaro. A associação do polimorfismo C677T e o perfil de Hbs foram estudados em 683 RNs, apresentando freqüência elevada da coexistência do alelo T e Hb variantes. Estes resultados podem ser utilizados como base para estudos futuros sobre riscos potenciais de eventos vaso-oclusivos nestes indivíduos.

The C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) is associated with an increase in total homocysteine serum levels (tHcy), described as a risk factor for cardiovascular disease. Eight hundred forty-three neonates from two different maternity hospitals, one public and another private, in Salvador, Bahia, Brazil were screened for this polymorphism by PCR and RFLP. The T-allele frequency in the total sample was 0.23, and the prevalence rates of heterozygous and homozygous carriers were 36.2% and 5.3%, respectively. The T-allele frequency differed and the T/T genotype was more prevalent at the private maternity hospital. The hemoglobin (Hb) profile was investigated by HPLC in 763 newborns. The frequency of variant Hb was higher at the public than at the private maternity hospital. The association of the C677T polymorphism and the Hb profile was investigated in 683 newborns, showing a relatively high frequency of variant Hbs and the T allele. These data could provide an important basis for further studies focusing on potential risks of vaso-occlusive events in these individuals.