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Introdução: A anemia por deficiência de ferro em crianças em idade pré-escolar apresenta elevada prevalência no mundo e no Brasil. Objetivos: Avaliar a ocorrência de fatores associados à anemia em crianças de 6 a 59 meses atendidas na Estratégia Saúde da Família do município de Governador Valadares, MG. Métodos: Realizou-se um estudo transversal exploratório analítico com 91 crianças, entre os anos de 2014 e 2016, tendo sido avaliadas condições socioeconômicas da família, de saúde materna durante a gestação e de vida e saúde da criança, estado nutricional, frequência de consumo de alimentos fonte de ferro e recebimento de informações sobre a anemia. A regressão logística multinomial foi utilizada para determinar fatores associados à anemia, considerando-se significante quando p< 0,05. Resultados: A ocorrência da anemia foi verificada em 26,4% das crianças sendo que, considerando-se apenas as crianças com 6 a 24 meses, 40% apresentavam anemia. Verificou-se associação positiva da anemia com o aleitamento materno por 12 meses ou mais, recebimento de orientações sobre anemia, maior frequência semanal de consumo de fígado, e maior ocorrência de higiene das mãos antes das refeições por parte da mãe/responsável. Ainda, o aumento da idade da criança se associou negativamente à ocorrência desta doença. Conclusão: Apesar de apenas a associação negativa com a idade corroborar os dados da literatura, os resultados aqui descritos indicam elevada ocorrência de anemia principalmente nas crianças de 6-24 meses e a necessidade de ações de prevenção da anemia e de protocolos para diagnóstico precoce de deficiência de ferro.

Objectives: to evaluate the use of iron supplementation and associated factors in children aged six to 59 months attended at the Family Health Strategy units in a city in Minas Gerais (MG). Methods: a cross-sectional, analytical-exploratory study, carried out with 252 children aged six to 59 months, attended at ten units, between 2014 and 2016. A structured questionnaire was used to collect data on socioeconomic conditions, maternal health, child’s health and the knowledge of those responsible regarding anemia and iron supplementation, in addition to analysis of the child’s medical records /booklet to collect test results. Descriptive statistics, bivariate association analysis and logistic regression for multivariate analysis were performed. Results: only 22.6% of the children aged between six and 24 months were receiving iron supplement at the time of the interview. Considering children aged six to 59 months, 13.1% were supplemented and breastfeeding time (p=0.006) and the participation in childcare (p=0.042), were positively associated with the use of supplementation. Conclusion: most children aged six to 24 months were not receiving supplementation as recommended by the Ministry of Health, demonstrating the need to implement prevention programs, such as the National Iron Supplementation Program and training of professionals on the importance of health education in preventing childhood anemia. Resumo Objetivos: avaliar o uso do suplemento de ferro e fatores associados em crianças de seis a 59 meses atendidas em unidades Estratégia Saúde da Família em município de Minas Gerais (MG). Métodos: estudo transversal, analítico-exploratório, realizado com 252 crianças na faixa etária seis a 59 meses, atendidas em dez unidades, entre 2014 e 2016. Utilizou-se questionário estruturado para coleta de dados sobre condições socioeconômicas, saúde materna, saúde da criança e conhecimentos dos responsáveis acerca da anemia e suplementação com ferro, além de análise do prontuário / caderneta da criança para coleta de resultados de exames. Realizou-se análise estatística descritiva, análise de associação bivariada e regressão logística para análise multivariada. Resultados: apenas 22,6% das crianças com idade entre seis e 24 meses estavam recebendo o suplemento de ferro no momento da entrevista. Considerando as crianças de seis a 59 meses, 13,1% eram suplementadas e o tempo de amamentação (p=0,006) e a participação na puericultura (p=0,042) apresentaram associação com o uso de suplemento. Conclusão: a maioria das crianças de seis a 24 meses não recebia a suplementação, demonstrando a necessidade de implementação dos programas de prevenção, como o Programa Nacional de Suplementação de Ferro e capacitação dos profissionais sobre a importância da educação em saúde para prevenção da anemia infantil.

Polycythemia vera (PV) is a clonal disorder resulting from neoplastic transformation of hematopoietic stem cells, while secondary polycythemia (SP) is a disease characterized by increased absolute red blood cell mass caused by stimulation of red blood cell production. Although the physiopathology of SP and PV is distinct, patients with these diseases share similar symptoms. The early differential diagnosis may improve the quality of life and decrease the disease burden in PV patients, as well as enable curative treatment for SP patients. PV is considered an oncoinflammatory disease because PV patients exhibit augmented levels of several pro-inflammatory cytokines. In this sense, we examined whether analysis of the cytokine production profile of SP and PV patients would help to distinguish them, despite their clinical similarities. Here we reported that SP patients exhibited decreased plasma levels of, IL-17A, IFN-γ, IL-12p70 and TNF-α when compared with PV patients, suggesting that analysis of the cytokine production profile may be an useful diagnostic biomarker to distinguish PV from SP patients.

Myeloproliferative neoplasms (MPN) are hematological disorders characterized by increased proliferation of precursor and mature myeloid cells. MPN patients may present driver mutations in JAK2, MPL, and CALR genes, which are essential to describe the molecular mechanisms of MPN pathogenesis. Despite all the new knowledge on MPN pathogenesis, many questions remain to be answered to develop effective therapies to cure MPN or impair its progression to acute myeloid leukemia. The present study examined the expression levels of the Hippo signaling pathway members in patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), as well as the role that they play in disease pathogenesis. The Hippo pathway is a tumor suppressor pathway that participates in the regulation of cell proliferation, differentiation, and death. Our main findings were: (i) expression of tumor suppressor genes from Hippo pathway were downregulated and seemed to be associated with cell resistance to apoptosis and increased proliferation rate; and (ii) Hippo pathway-related gene expression was associated with mutation status in ET and PMF patients. Therefore, the decreased expression of Hippo pathway-related genes may contribute to the malignant phenotype, apoptosis resistance, and cell proliferation in MPN pathogenesis.

Myeloproliferative neoplasms polycythemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis constitute a group of haematological diseases. The comprehensive assessment of signaling pathway activation in blood cells may aid the understanding of MPN pathophysiology. Thus, levels of post-translational protein modifications and total protein expression were determined in MPN patients and control leukocytes by using reverse-phase protein arrays (RPPA). Compared to control samples, p-SRC, p-CTNNB1, c-MYC, MCL-1, p-MDM2, BAX and CCNB1 showed higher expression in PV samples than controls. P-JAK2/JAK2 and pro-apoptotic BIM showed differential expression between JAK2V617F-positive and -negative ET patients. Apoptosis, cancer and PI3K/AKT pathways proteins showed differential expression among the studied groups. For most of the proteins analyzed using Western-Blot and RPPA, RPPA showed higher sensitivity to detect subtle differences. Taken together, our data indicate deregulated protein expression in MPN patients compared to controls. Thus, RPPA may be a useful method for broad proteome analysis in MPN patients´ leukocytes.

Introdução: A introdução da alimentação complementar de forma adequada e a formação de hábitos alimentares saudáveis são grandes desafios no Brasil, onde muitos alimentos importantes para o desenvolvimento das crianças não lhe são ofertados devido a crenças, tabus e culturas regionais, bem como acesso e disponibilidade. Alguns desses alimentos atuam diretamente na prevenção da anemia ferropriva, como carnes e vísceras, folhas verdes em geral, feijões e gema de ovo. Objetivo: Avaliar a frequência de consumo de alimentos fonte de ferro entre crianças de 6 a 59 meses cadastradas na Estratégia de Saúde da Família. Material e Métodos: Trata-se de estudo transversal realizado com 256 crianças de 6 a 59 meses cadastradas na Estratégia de Saúde da Família de um município no interior do estado de Minas Gerais. Aplicou-se questionário estruturado sobre condições de vida e saúde e frequência alimentar e avaliaram-se dados antropométricos. Utilizaram-se testes de Mann-Whitney e qui-quadrado de Pearson na comparação dos resultados segundo faixa etária da criança, adotando-se p

Cytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms.This study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters.The proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JAK2 V617F mutation was associated with high IP-10 levels in primary myelofibrosis patients.Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms.

The pathogenesis and clinical outcomes of myeloproliferative neoplasms (MPN) involve genetic and molecular anomalies. The most prevalent somatic mutation in polycythemia vera (PV), essential thromb...

Background/Aims: We investigated the effects of tyrosine kinase inhibitors (TKIs) on the expression of apoptosis-related genes (BCL-2 and death receptor family members) in chronic myeloid leukemia (CML) patients. Methods: Peripheral blood mononuclear cells from 32 healthy subjects and 26 CML patients were evaluated before and after treatment with imatinib mesylate (IM) and dasatinib (DAS) by quantitative PCR. Results: Anti-apoptotic genes (c-FLIP and MCL-1) were overexpressed and the pro-apoptotic BIK was reduced in CML patients. Expression of BMF, A1, c-FLIP, MCL-1, CIAP-2 and CIAP-1 was modulated by DAS. In IM-resistant patients, expression of A1, c-FLIP, CIAP-1 and MCL-1 was upregulated, and BCL-2, CIAP-2, BAK, BAX, BIK and FASL expression was downregulated. Conclusion: Taken together, our results point out that, in CML, DAS interferes with the apoptotic machinery regulation. In addition, the data suggest that apoptosis-related gene expression profiles are associated with primary resistance to IM.

As neoplasias mieloproliferativas crônicas cromossomo Filadélfia negativas são doenças hematológicas clonais que se caracterizam pela independência ou pela hipersensibilidade dos progenitores hematopoiéticos às citocinas. Os mecanismos celulares e moleculares envolvidos na fisiopatologia das neoplasias mieloproliferativas crônicas ainda não estão totalmente esclarecidos. Achados fisiopatológicos relevantes para as neoplasias mieloproliferativas crônicas estão associados às alterações genéticas como, por exemplo, a mutação somática no gene que codifica o JAK2 (JAK2V617F). A desregulação do processo de morte celular programada, denominada apoptose, parece participar da patogênese dessas desordens. Sabe-se que a desregulação da expressão dos genes pró- e antiapoptóticos promove a resistência das células à apoptose, culminando com o acúmulo das células mieloides e estabelecendo a neoplasia. Esta revisão enfocou as alterações na regulação da apoptose em neoplasias mieloproliferativas crônicas e a importância da melhor compreensão desse mecanismo para o desenvolvimento de novas terapias para essas doenças. Philadelphia-chromosome negative chronic myeloproliferative neoplasms are clonal hematologic diseases characterized by hematopoietic progenitor independence from or hypersensitivity to cytokines. The cellular and molecular mechanisms involved in the pathophysiology of myeloproliferative neoplasms have not yet been fully clarified. Pathophysiologic findings relevant for myeloproliferative neoplasms are associated with genetic alterations, such as, somatic mutation in the gene that codifies JAK-2 (JAK V617F). Deregulation of the process of programmed cellular death, called apoptosis, seems to participate in the pathogenesis of these disorders. It is known that expression deregulation of pro- and anti-apoptotic genes promotes cell resistance to apoptosis, culminating with the accumulation of myeloid cells and establishing neoplasms. This review will focus on the alterations in apoptosis regulation in myeloproliferative neoplasms, and the importance of a better understanding of this mechanism for the development of new therapies for these diseases.

MicroRNAs are small non-coding RNAs that inhibit posttranscriptional gene expression through deadenylation and cleavage. Th ese molecules play crucial roles in regulating cell diff erentiation, proliferation and apoptosis [1]. MicroRNA expression levels are strongly associated with numerous human pathogenic diseases [2]. Th us, the discovery of microRNAs has opened up a wide range of possibilities regarding the understanding of disease pathophysiology and the development of new therapeutic agents. Recent studies show that microRNAs may participate in the regulation of apoptosis machinery (apoptomiRs). Apoptosis is a programmed cell death, orchestrated by the BCL-2 protein family, death receptors and inhibitor of apoptosis proteins (IAPs) [3]. Deregulated apoptosis is associated with tumorigenesis and autoimmunity [3] and seems to contribute to myeloproliferative neoplasms (MPNs), which are clonal disorders characterized by myeloaccumulation and in most cases by the presence of a somatic mutation in Janus kinase 2 (JAK2) [4]. Our research group previously described abnormal apoptosis in patients with MPNs [5 – 7]. We found abnormal expression of death-receptor pathway-related genes such as FAIM and C-FLIP in leukocytes and CD34 � hematopoietic stem cells (HSCs) [5], and deregulation of BCL-2 family members associated with JAK2 mutation [6,7]. Th ese fi ndings led us to investigate the molecular mechanisms associated with apoptosis deregulation in patients with MPNs. In this study, we sought to identify microRNAs whose targets are apoptosis-related genes, investigate their expression in patients with MPNs, and correlate this with the expression of apoptosis-related genes and JAK2 mutation allele burden using three algorithms (websites: http://www.diana.pcbi. upenn.edu/cgi-bin/miRGen/v3/Targets.cgi; Microcosm Targets: http://www.ebi.ac.uk/enright-srv/microcosm/cgi-bin/ targets/v5/hit_list.pl?genome_id � 2964; and Target Scan: http://www.targetscan.org). Th e microRNAs and their respective target genes (apoptosis-related genes) predicted by the bioinformatics tools are as follows: miR-15a: BIK and BCL-2; miR-16: BID, BIK, BCL-2 and BCL xl; miR-26a: C-FLIP, CIAP-2 and MCL-1; miR-130b: CIAP-2; miR-21: CIAP-2, FASL and BCL-2; miR-29c: CIAP-1 and MCL-1; and miR-let-7d: A1, BAX, FAS and FASL. In this study, we investigated apoptomiRs miR-26a, -130b, -21, -29c, -let-7d, -15a and -16. We quantifi ed their expression in bone marrow CD34 � HSCs and peripheral blood leukocytes in 27 patients with polycythemia vera (PV), 25 with essential thrombocythemia (ET) and 12 with primary myelofi brosis (PMF) (26 males and 38 females, mean age: 60.5 years). Th e bone marrow control group comprised 14 bone mar

Despite all the knowledge, the cellular and molecular mechanisms involved in myeloproliferative neoplasm (MPN) pathophysiology remain unclear. Authors have shown galectin-1 (Gal-1) and 3 playing roles in tumour angiogenesis and fibrosis, which were correlated with poor prognosis in patients with MPN. In the present study LGALS1 and LGALS3 were differently expressed between polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF) diseases. Increased LGALS3 expression was associated with a negative JAK2 V617F status mutation in leucocytes from PMF but not in patients with ET without this mutation. However, a positive Janus kinase 2 (JAK2) V617F cell line established from patients with ET (SET-2 cells) when treated with JAK inhibitor presented high levels of LGALS3. Additionally, high LGALS1 expression was found in CD34(+) cells but not in leucocytes from patients with PMF, in absence of JAK2 V617F mutation, and also in SET-2 cells treated with JAK inhibitor. Thus, our findings indicate that differential expression of LGALS1 and/or LGALS3 in patients with MPN is linked with JAK2 V617F status mutation in these diseases and state of cell differentiation.

Summary Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells, resulting in insulin deficiency and hyperglycaemia. Recent studies have described that apoptosis impairment during central and peripheral tolerance is involved in T1D pathogenesis. In this study, the apoptosis-related gene expression in T1D patients was evaluated before and after treatment with high-dose immunosuppression followed by autologous haematopoietic stem cell transplantation (HDI-AHSCT). We also correlated gene expression results with clinical response to HDI-AHSCT. We observed a decreased expression of bad, bax and fasL pro-apoptotic genes and an increased expression of a1, bcl-xL and cIAP-2 anti-apoptotic genes in patients' peripheral blood mononuclear cells (PBMCs) compared to controls. After HDI-AHSCT, we found an up-regulation of fas and fasL and a down-regulation of anti-apoptotic bcl-xL genes expression in post-HDI-AHSCT periods compared to pre-transplantation. Additionally, the levels of bad, bax, bok, fasL, bcl-xL and cIAP-1 genes expression were found similar to controls 2 years after HDI-AHSCT. Furthermore, over-expression of pro-apoptotic noxa at 540 days post-HDI-AHSCT correlated positively with insulin-free patients and conversely with glutamic acid decarboxylase autoantibodies (GAD65) autoantibody levels. Taken together, the results suggest that apoptosis-related genes deregulation in patients' PBMCs might be involved in breakdown of immune tolerance and consequently contribute to T1D pathogenesis. Furthermore, HDI-AHSCT modulated the expression of some apoptotic genes towards the levels similar to controls. Possibly, the expression of these apoptotic molecules could be applied as biomarkers of clinical remission of T1D patients treated with HDI-AHSCT therapy.

As Neoplasias Mieloproliferativas Crônicas (NMPC) Trombocitemia Essencial (TE), Mielofibrose (MF) - são desordens hematopoéticas resultantes da expansão clonal da célula tronco hematopoética alterada. Essas doenças caracterizam-se pela independência dos progenitores hematopoéticos aos estímulos dos fatores de crescimento e citocinas e pela proliferação exacerbada das células da linhagem mielóide com maturação preservada. Os mecanismos moleculares e celulares envolvidos na patogênese e progressão da TE e MF não foram ainda esclarecidos, mas o mieloacúmulo presente nessas doenças parece estar associado à alteração de proliferação e apoptose celular. Nesse contexto, os objetivos deste trabalho foram avaliar em células CD34+ da medula óssea e leucócitos dos pacientes com TE e MF: (1) a expressão de apoptomirs e de genes pró- e anti-apoptóticos pertencentes à via intrínseca e extrínseca da apoptose pela metodologia de RT-PCR em tempo real; (2) expressão de proteínas pró- e anti-apoptóticas por Western-blot; (3) o perfil de sensibilidade das células mononucleares à apoptose induzida por diferentes agentes apoptogênicos pela técnica de citometria de fluxo e (4) correlacionar os resultados obtidos com dados clínico-laboratoriais dos pacientes e com a expressão do gene PRV-1. Em TE, nas células CD34+, foi detectado aumento da expressão de a1, mcl-1, bid, bok e noxa e diminuição de bax em relação aos controles. Nos leucócitos, foi detectada a elevação da expressão de a1, bcl-2, bcl-w e bcl-xL, bad e bok e diminuição de bid e bimEL. Em comparação com o grupo controle, os pacientes com MF apresentaram maior expressão dos genes a1, bcl-w bak, bok e noxa e menor de bcl-2 nas células CD34+. Nos leucócitos dos pacientes com MF foi verificado aumento da expressão dos genes bcl-2, bcl-w e bcl-xL, bad e bok. O c-iap-1 apresentou maior expressão nas células CD34+ dos pacientes com MF e TE, enquanto que o c-iap-2 estava elevado nos leucócitos e células CD34+. Foi ainda detectada a expressão diferencial em TE e MF dos genes pertencentes a via de receptor de morte, como a maior expressão dos genes fas, fas-L, faim e dr4 nas células CD34+ dos pacientes e menor expressão do fas-L e trail nos leucócitos dos pacientes com TE e MF. Os resultados indicaram associação da expressão do gene PRV-1 com a mutação JAK2V617F e com a expressão dos genes a1, bcl-w, bik, bax, c-iap-2 e trail. Com relação à expressão proteica, BCL-XL estava aumentada e TRAIL diminuída em leucócitos de pacientes com MF enquanto que a molécula BID estava diminuída em leucócitos de pacientes com TE. Os miRNA26a, let 7d e miR15a estavam mais expressos nos leucócitos de pacientes com TE e MF. Em pacientes com TE o miR130b estava elevado e o mIR16 diminuído, enquanto que nos pacientes com MF o miR198 estava aumentado. Os linfócitos dos pacientes com TE e MF apresentaram maior resistência à apoptose estimulada por: actinomicina, etoposídeo, teniposídeo, citarabina e estaurosporina do que os linfócitos dos controles. Em conclusão, os dados obtidos sugerem a ligação da alteração do processo de apoptose celular, com a expressão do gene PRV-1 e status da mutação JAK2V617F. Esses resultados contribuem para o melhor entendimento da fisiopatologia das NMPC visto que associam a fisiopatologia da TE e MF com a resistência das células alteradas à apoptose. Essas informações serão úteis no futuro, possibilitando o desenho de novos alvos terapêuticos e a descrição de novos marcadores de prognóstico. Chronic Myeloproliferative Neoplasms (cMPN) - Essential Thrombocythemia (ET), Primary Myelofibrosis (PMF) and Polycythemia Vera (PV) - are clonal hematopoietic stem cell malignancies characterized by an accumulation of mature myeloid cells in bone marrow and peripheral blood. It seems that apoptotic machinery deregulation contribute to ET and PMF pathogenesis. Despite the advances in the molecular knowledge, the physiopathology of these diseases remains unknown. This study investigated cellular and molecular mechanisms involved in apoptosis process regulation in bone marrow haematopoietic progenitor CD34+ cells and leukocytes from ET and PMF patients. The specifics aims were: (1) to evaluate death receptors family members and Bcl-2 related genes expression as well apoptosis-related microRNAs by Real Time PCR; (2) apoptosis-related protein expression by Western Blot; (3) access mononuclear cells apoptosis resistance by flow cytometry and (4) to correlate the results with JAK2V617F mutation, PRV-1 gene expression and as well clinical data. In ET CD34+ cells, we found overexpression of a1, mcl-1, bid, bok e noxa and a decrease of bax compared to controls, while in leukocytes a1, bcl-2, bcl-w e bcl-xL, bad e bok expression was increased and bid and bimEL expression was lower than in controls. In PMF, a1, bcl-w bak, bok e noxa were overexpressed and bcl-2 downregulated in CD34+ cells. In PMF leukocytes bcl-2, bcl-w e bcl-xL, bad e bok mRNA levels were increased. c-iap-1 was increased in ET and PMF CD34+ cells and c-iap-2 expression elevated in ET and PMF CD34+ cells and leukocytes. Death receptor related genes showed overexpression of fas, fas-L, faim and dr4 in patients CD34+ cells and downregulation of fas-L and trail in ET and PMF leukocytes. We found differential expression of several genes between patients JAK2V617F positive and negative, as well we found correlation between gene expression and JAK2V617F allele burden, white blood cells and platelets count and splenomegaly. PRV-1 gene was overexpressed in ET and PMF leukocytes and showed correlation with JAK2V617F mutation and a1, bcl-w, bik, bax, c-iap-2 and trail gene expression. Regarding protein expression, BCL-XL was increased and TRAIL decreased in PMF leukocytes and BID was decreased in ET leukocytes. miRNA26a, let 7d e miR15a was overexpressed in ET and PMF leukocytes, while miR130b was increased only in ET and miR198 only in PMF. miR16 was downregulated in ET leukocytes comparing to controls. We also detected a resistance to apoptosis-inducers in ET and PMF lymphocytes and we observed correlation between apoptosis percentage and the expression of many studied genes. In conclusion, the results indicate the participations of Bcl-2 family genes and Death Receptor pathway genes, as well PRV-1 and JAK2V617F mutation in these disorders, which contribute to elucidate cMPN physiopathology and might lead to the discovery of new cMPN therapies and molecular markers.

A anemia ferropriva (AF) é uma doença multifatorial e responde pela maior parte dos casos de anemia em crianças de 6 a 59 meses, estando muito relacionada com fatores biológicos, socioeconômicos e nutricionais. Se instaura de forma gradativa e seus sinais e sintomas são inespecíficos como: cansaço, fraqueza muscular e palidez. Possui consequencias como baixo crescimento ponderal e estatural, dificuldade de aprendizagem e queda da imunidade. No Brasil, a anemia infantil ainda é um problema de saúde pública devido a sua alta prevalência de, em média, 40%. O presente trabalho teve como objetivo avaliar a prevenção da anemia e orientar os responsáveis por crianças de 6-59 meses cadastradas em unidades Estratégia Saúde da Família (ESF) do município de Governador Valadares, MG. Foram realizadas entrevistas estruturadas contendo questões sobre o conhecimento com relação à anemia, recebimento de orientações, participação nas atividades de puericultura na ESF e suplementação de ferro (SF). Foram consultados os prontuários para obtenção de resultados de exames hematológicos e bioquímicos. Ao final, foram dadas orientações sobre a AF e medidas para prevenção e tratamento. Dos 209 responsáveis entrevistados, 42,6% relataram desconhecer os sintomas da anemia, sendo que 70,8% relataram que nunca receberam orientação profissional sobre anemia. Além disso, apenas 46,2% das crianças participavam ou haviam participado da puericultura na ESF. Dentre as 88 crianças de 6-59 meses que haviam realizado hemograma em um intervalo máximo de 3 meses antes ou depois da entrevista, a prevalência da anemia (Hb

Philadelphia-chromosome negative chronic myeloproliferative neoplasms are clonal hematologic diseases characterized by hematopoietic progenitor independence from or hypersensitivity to cytokines. The cellular and molecular mechanisms involved in the pathophysiology of myeloproliferative neoplasms have not yet been fully clarified. Pathophysiologic findings relevant for myeloproliferative neoplasms are associated with genetic alterations, such as, somatic mutation in the gene that codifies JAK-2 (JAK V617F). Deregulation of the process of programmed cellular death, called apoptosis, seems to participate in the pathogenesis of these disorders. It is known that expression deregulation of pro- and anti-apoptotic genes promotes cell resistance to apoptosis, culminating with the accumulation of myeloid cells and establishing neoplasms. This review will focus on the alterations in apoptosis regulation in myeloproliferative neoplasms, and the importance of a better understanding of this mechanism for the development of new therapies for these diseases.

Background Chronic myeloproliferative disorders (MPDs) are clonal haematopoietic stem cell malignancies characterised by an accumulation of mature myeloid cells in bone marrow and peripheral blood. Deregulation of the apoptotic machinery may be associated with MPD physiopathology. Aims To evaluate expression of death receptors9 family members, mononuclear cell apoptosis resistance, and JAK2 allele burden. Subjects and Methods Bone marrow haematopoietic progenitor CD34 cells were separated using the Ficoll-hypaque protocol followed by the Miltenyi CD34 isolation kit, and peripheral blood leukocytes were separated by the Haes-Steril method. Total RNA was extracted by the Trizol method, the High Capacity Kit was used to synthesise cDNA, and real-time PCR was performed using SybrGreen in ABIPrism 7500 equipment. The results of gene expression quantification are given as 2 −ΔΔCt . The JAK2 V617F mutation was detected by real-time allelic discrimination PCR assay. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-hypaque protocol and cultured in the presence of apoptosis inducers. Results In CD34 cells, there was mRNA overexpression for fas , faim and c-flip in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), as well as fasl in PMF, and dr4 levels were increased in ET. In leukocytes, fas , c-flip and trail levels were increased in PV, and dr5 expression was decreased in ET. There was an association between dr5 and fasl expression and JAK2V617F mutation. PBMCs from patients with PV, ET or PMF showed resistance to apoptosis inducers. Conclusions The results indicate deregulation of apoptosis gene expression, which may be associated with MPD pathogenesis leading to accumulation of myeloid cells in MPDs.

Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV). This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005). CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively) in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020); while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19) compared with controls (1.39 and 2.01, p=0.006 and p=0.020). CD34+ cells in PV patients showed an elevated Bid expression (14.4) in comparison with healthy subjects (1.0; p=0.002). Patients' leukocytes showed an A1 augmentation (7.41, p=0.001) and a reduced expression of Bax (0.19; p=0.040) and Bad (0.2; p=0.030). There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV). Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005). Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente) em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020) e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19) em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0,020). Células CD34 + dos pacientes com PV mostraram expressão elevada de bid (14,4) em comparação aos controles (1,0; p = 0,002). Leucócitos dos pacientes mostraram aumento de A1 (7,41, p = 0,001) e expressão reduzida do Bax (0,19; p = 0,04) e Bad (0,2; p = 0,030). Não houve correlação entre percentagem de alelos JAK2 V617F mutados e expressão molecular. Pacientes com PV apresentaram alterações na expressão de moléculas Bcl-2 que podem interferir no controle da apoptose e contribuir para a patogênese da doença.

Abstract 5057 Background: Polycythaemia vera (PV) is a clonal disorder characterized by an accumulation of normal red and white cells, platelets, and their progenitors in absence of a definable stimulus. Despite the advances in PV diagnosis its physiopathology remains not well elucidated. Apoptosis deregulation seems to contribute to disease establishment. MicroRNAs are small noncoding RNAs, post transcriptional repressors of genes by deadenilation, which play relevant roles in regulation of apoptotic machinery. Here we investigate the relation of apoptosis deregulation and apoptomirs expression in PV patients. Aims: To quantify the apoptomirs −16, −21, −15a, −26a, 130b, 29c and let-7d expression in peripheral leukocytes and CD34+ hematopoietic stem cells (HSC) in Polycythemia Vera (PV) patients and to correlate with targets genes expression data. Subjects and Methods: 30 PV patients, 13 men and 17 women with a mean age (ma) of 64. 7y. 30 healthy subjects, 13 males and 17 females, ma=60. 2y and 23 bone marrow donors, 14 males and 9 females, ma=32. 6y. Peripheral leukocytes were obtained by Haes-Steril method and CD34+ hematopoietic stem cells were enriched by using the magnetically activated cell sorting, total RNA was extracted according to Trizol® method and High Capacity® Kit was used to synthesize cDNA. The microRNAs and apoptosis-related genes expression quantification was performed by real time PCR. Results were given as 2-ΔΔCt and statistical analyses were carried out by Mann-Whitney and Spearman tests. Western Blot was applied to detect Bcl-2 protein expression. Results: miR-16 and miR21 levels were increased in PV leukocytes (median= 3. 45 and 6. 97 respectively)) and CD34+ HSC (median= 3. 86 and 4. 07 respectively) in comparison to controls (control leukocytes median= 0. 483 and 0. 989 respectively) (CD34+ HSC median= 0. 978 and 1. 15, respectively) (p= 0. 0001 and 0. 0001 in leukocytes) and (p= 0. 0001 and 0. 0005 in CD34+ HSC, respectively). The Bcl-2 gene expression was decreased in PV leukocytes (m= 0.18) when compared to controls (m= 1. 03; p= 0. 019). In addition we found in CD34+ HSC negative correlation between miR-21 and anti-apoptotic gene Bcl-2 (r= −0. 417; p= 0. 033) and between miR16 and anti-apoptotic gene Bcl-2(r= −0. 384; p=0. 046). Bcl-2 western blot showed half expression in PV leukocytes when compared to controls. Conclusions: The results indicate the apoptomirs expression is linked to apoptosis deregulation in Polycythemia Vera physiopathology. Disclosures: No relevant conflicts of interest to declare.

Background Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34+ hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters. Results By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34+ cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34+ cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-X L and BCLW. In contrast, pro-apoptotic BID and BIM EL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly. Conclusions Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.

FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais Estudos ainda são controversos a respeito de diferenças entre os indivíduos com anemia falciforme (AF) e da doença SC (HbSC), principalmente em relação a associação do estado nutricional com marcadores de gravidade. O ângulo de fase (AngF), uma medida de integridade de membrana celular, correlacionou-se com o prognóstico em diferentes situações clínicas, entretanto ainda são limitadas suas informações na doença falciforme (DF). A dislipidemia na DF é variável e existem poucos estudos indicando sua relação com a gravidade e com variantes genéticas envolvidas na homeostase lipídica. O objetivo do estudo foi avaliar biomarcadores clínicos, nutricionais, laboratoriais e moleculares em indivíduos com DF (AF e HbSC), o potencial do AngF como preditor de gravidade da AF, a influência das variantes e haplótipos do gene CETP, bem como associações entre as variáveis e as diferenças entre os dois genótipos da DF. O estudo ocorreu com crianças e adolescentes com DF (AF e HbSC) acompanhados no Hemocentro de Governador Valadares da Fundação Hemominas. Coletaram-se os dados demográficos, socioeconômicos, clínicos, antropométricos, bioimpedância elétrica e laboratoriais (vitaminas A e D, marcadores do perfil lipídico e de gravidade) de 138 participantes, sendo 75 com AF (54,35%) e 63 com HbSC (45,65%) com idade média de 11,63 anos. Nas análises envolvendo o AngF, participaram 64 pacientes com AF e o mesmo número em um grupo sem doença falciforme (SDF) com idade média de 12,27 e 11,47 anos respectivamente. Foram genotipados a α-talassemia (α-tal) e polimorfismos no gene CETP (rs247616, rs183130 e rs3764261). Os valores do AngF foram determinados e comparados entre os grupos SDF e AF, sendo investigada a sua relação com marcadores de gravidade na AF. O grupo AF apresentou maior deficit nutricional, hipocolesterolemia e anemia mais acentuadas, como também maior gravidade indicada pelos marcadores hemolíticos e inflamatórios em comparação ao grupo HbSC. Na AF, índice de massa corporal (IMC), vitamina A, lipoproteína de alta densidade (HDL-C) e apolipoproteína A1 (apoA1) foram inversamente correlacionados com leucócitos totais (LT), lactato desidrogenase (LDH) e/ou bilirrubina total (BT). A hemoglobina (Hb) foi associada de forma positiva com a vitamina A e de forma negativa com os triglicerídios (TG). Na DF, indivíduos com α-tal apresentaram menores valores de volume corpuscular médio (VCM) e hemoglobina corpuscular média (HCM). O valor do AngF foi menor nos indivíduos AF e nesses houve associação com marcadores de gravidade da doença. Indivíduos com AF em uso de Hidroxiureia apresentaram maiores valores de HDL-C, entretanto, não houve associação entre essas variáveis. A ausência do haplótipo TTA dos SNPs (rs247616, rs183130 e rs3764261) do gene CETP aumentou em 3 vezes risco de ter baixos níveis de HDL-C nos pacientes com DF. Adicionalmente, os baixos níveis de Hb também conferiram risco para menores valores desta lipoproteína para estes pacientes e ao analisar somente o grupo AF. O estudo concluiu que o grupo AF apresentou maior gravidade em comparação ao grupo HbSC ao considerar perfil nutricional e gravidade da doença. O estado nutricional foi associado com os marcadores de gravidade, principalmente na AF. O AngF mostrou-se uma variável promissora na predição da gravidade da AF. Variantes do gene CETP somados aos fatores intrínsecos da própria anemia hemolítica poderiam explicar parte da variação observada na dislipidemia em pacientes com DF. Studies are still controversial regarding differences between individuals with sickle cell anemia (SCA) and SC disease (HbSC), mainly in relation to the association of nutritional status with severity markers. Phase angle (PhA), a measure of cell membrane integrity, correlates with prognosis in different clinical situations; however, there is still limited information about its correlation with prognostics in sickle cell disease (SCD). Dyslipidemia in SCD is variable and there are few studies indicating a relationship with the severity and genetic variants involved in lipid homeostasis. The aims of this study was to evaluate clinical, nutritional, laboratory and molecular biomarkers in individuals with SCD (SCA and HbSC), the potential of PhA as a predictor of SC severity, the influence of CETP gene variants and haplotypes, as well as associations between the variables and the differences between the two genotypes of SCD. The study has been conducted with children and adolescents with SCD (SCA and HbSC) followed in the blood center of Governador Valadares of the Hemominas Foundation. Demographic, socioeconomic, clinical, anthropometric, laboratory (vitamins A and D, lipid profile and severity markers) and electrical bioimpedance data were collected. Of the 138 participants, 75 had SCA (54.3%) and 63 HbSC (45.7%), with a mean age of 11.63 years. Sixty-four patients with SCA participated in the analyzes involving PhA and the same number in the group without sickle cell disease (WSCD), with an average age of 12.27 and 11.47 years, respectively. The αthalassemia (α-thal) and the polymorphisms in the CETP gene (rs247616, rs183130 and rs3764261) were genotyped. PhA values were defined and compared between WSCD and SCA groups and the relationship of this measure with severity markers in SCA was investigated. Group SCA exhibited higher nutritional deficit, more severe hypocholesterolemia and anemia, as well as greater severity indicated by hemolytic and inflammatory markers compared to group HbSC. In SCA, body mass index, vitamin A, high-density lipoprotein (HDL-C) and apolipoprotein A1 (apoA1) showed an inverse correlation with total leukocytes, lactate dehydrogenase (LDH) and/or total bilirubin (TB). Hemoglobin (Hb) was positively associated with vitamin A and negatively associated with triglycerides (TG). In SCD, individuals with αthal exhibited lower values for the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). The PhA value was lower in the SCA individuals and showed association with markers of disease severity. Subjects with SCA using Hydroxyurea had higher levels of HDL-C, however, there was no association between these variables. The absence of the SNP TTA haplotype (rs247616, rs183130 and rs3764261) of the CETP gene tripled the risk of having low HDL-C levels in patients with SCD. In addition, the low levels of Hb also led to risk of low values of this lipoprotein in these patients when analyzing only the SCA group. The study concluded that the SCA group had worse condition compared to the HbSC group when considering nutritional profile and disease severity. Nutritional status was associated with severity markers, especially in SCA. The PhA proved to be a promising variable in predicting the severity of SCA. Variants of the CETP gene together with the intrinsic factors of the hemolytic anemia itself could explain part of the variation observed in dyslipidemia in patients with SCD

A anemia falciforme (AF) apresenta manifestações clínicas graves e multissistêmicas. As complicações da AF são inversamente proporcionais às concentrações de hemoglobina fetal (HbF), entre outros fatores modificadores, com destaque para a co-herança de deleção da alfa-talassemia. Embora a AF não afete o crescimento embrionário, aos dois anos de idade pode-se notar um déficit no peso e estatura, que vai se acentuando progressivamente, com destaque maior na fase de adolescência, quando o atraso puberal faz acentuar a diferença entre o peso e altura das crianças comparadas aos controles saudáveis. O prejuízo no crescimento de crianças com AF inclui diversas causas, como a hipóxia tecidual, anemia, vasculopatia, desnutrição, infecções de repetição, hipogonadismo, deficiência na secreção do hormônio do crescimento (GH) ou alteração no eixo hormônio do crescimento/fator de crescimento semelhante à insulina (GH/IGF1). A terapia com hidroxiureia (HU) vem impactando na diminuição da morbimortalidade de adultos e crianças. Nesta pesquisa avaliou-se de forma longitudinal o perfil de crescimento, a eficácia da terapêutica com HU em atenuar os prejuízos no crescimento, o papel do eixo GH/IGF1 e a influência de fatores modificadores, como a HbF e alfa-talassemia, em crianças de 3 a 12 anos com AF. O estudo envolveu 39 pacientes cadastrados no Hemocentro de Governador Valadares da Fundação Hemominas com média de idade de 8,2 ± 2,2 anos, 51,3% (n = 20) do sexo masculino e 64,1% (n = 25) sob tratamento com HU. A prevalência de baixa estatura nas crianças foi de 10,3% (n = 4), embora entre os pais tenha sido de 14,4% (n = 11). O EZ da estatura das crianças foi -0,75 ± 1,1, sendo que 15,4% (n = 6) delas apresentaram níveis séricos de IGF1 ajustados pela idade cronológica (IC) abaixo da normalidade. Avaliando a diferença entre o EZ/estatura dos pais e EZ/estatura das crianças, encontramos maior prejuízo na estatura das crianças em relação ao alvo genético naquelas mais baixas, com menor previsão de estatura final (PEF) calculada por meio da idade óssea (IO) e co-herança de alfa-talassemia. Por outro lado, avaliando-se o eixo GH/IGF1 pelo EZ/IGF1 e EZ/IGFBP3 ajustados para a IC ou IO, observaram-se maior comprometimento do eixo nas crianças com menor índice de massa corporal (IMC), maior atraso na IO em relação à IC, maiores níveis séricos do hormônio estimulante da tireoide (TSH), menor estatura, menor nível de HbF, co-herança de alfa-talassemia e com menos tempo de uso da HU. Em conclusão, embora a estatura das crianças com AF não se mostrou prejudicada em relação à estatura dos pais, existe um grupo de crianças com maior comprometimento do seu potencial de crescimento. Entre os possíveis fatores associados ao comprometimento estatural nessa parcela das crianças com AF estão a co-herança de alfa-talassemia, menor proporção de HbF, maiores níveis de TSH, menor IMC, IO atrasada e o uso de HU por pouco tempo. Estes fatores mostraram associação com menor eficiência do eixo GH/IGF1. Sickle cell anemia (SCA) has severe and multisystem clinical manifestations. The complications of SCA are inversely proportional to fetal hemoglobin (HbF) concentrations, among other modifying factors, with emphasis on co-inheritance of alpha-thalassemia. Although the SCA does not affect embryonic growth, at two years of age can be noted a deficit in weight and stature, which will gradually accentuate, with greater prominence for the adolescence stage, when the pubertal delay accentuates the difference between the weight and height of children with SCA compared to healthy controls. Growth impairment of children with SCA includes several causes such as tissue hypoxia, anemia, vaso-occlusion, malnutrition, recurrent infections, hypogonadism, growth hormone (GH) deficiency or abnormalities in the growth hormone/insuline-like growth factor 1 (GH/IGF1) axis. Hydroxyurea (HU) therapy has been affecting the reduction of adult and child morbidity and mortality. In this research, we longitudinally evaluated the growth profile, the effectiveness of HU therapy in attenuating growth impairment, the role of the GH/IGF1 axis, and the influence of modifying factors, such as HbF and alpha-thalassemia, in children from 3 to 12 years with SCA. The study involved 39 patients registered in the unit blood center of Governador Valadares of the Hemominas Foundation with a mean age of 8.2 ± 2.2 years, 51.3% (n = 20) male and 64.1% (n = 25) under treatment with HU. The z-score of children's height was -0.75 ± 1.1, and 15.4% (n = 6) of them had serum IGF1 levels adjusted by chronological age (CA) below normal. The prevalence of short stature in children was 10.3% (n = 4), although among parents it was 14.4% (n = 11). Evaluating the difference between z-score/height of parents and z-score/height of children, we found greater impairment in height of children in relation to the genetic target in those with shorter height, lower prediction of final height (PFH) calculated by bone age (BA) and alpha-thalassemia co-inheritance. On the other hand, when the GH/IGF1 axis was assessed by the z-score/IGF1 and z-score/IGFBP3, adjusted for CA or BA, there was a significant greater impairment of the axis in children with lower body mass index (BMI), greater delay in BA compared to CA , higher serum levels of thyroid stimulating hormone (TSH), shorter stature, lower HbF level, co-inheritance of alpha-thalassemia and use of HU for a short period. In conclusion, although the height of children with SCA was not impaired in relation to the height of parents, there was a group of children with greater impairment of their growth potential. Among the possible factors associated with height impairment in this portion of children with AF are co-inheritance of alpha-thalassemia, lower HbF ratio, higher TSH levels, lower BMI, delayed BA, and use of UH for less than one year. These factors were associated with lower GH / IGF1 axis efficiency.

Hipocolesterolemia e hipertrigliceridemia são documentadas na Doença Falciforme (DF) há muitos anos, mas as causas e os efeitos na fisiopatologia ainda precisam ser esclarecidos. Além disto, relatos sobre marcadores genéticos relacionados ao metabolismo lipídico que explicam a variação dos níveis de lipídios e suas associações com os subfenótipos de hemólise e vaso-oclusão e com a variabilidade clínica da DF não foram publicados até o momento. O objetivo geral do estudo foi investigar se havia dislipidemia e se polimorfismos de um único nucleotídeo (SNPs) em genes ligados às variações lipídicas e inflamatórias estariam associados a alterações nas variáveis hematológicas, bioquímicas e clínicas, em crianças e adolescentes com as duas formas mais frequentes da DF, anemia falciforme (HbSS) e hemoglobinopatia SC (HbSC). A população consistiu de 155 indivíduos nascidos entre 2001 e 2010, com média de idade de 12,54 anos, sendo 55,5% do sexo masculino, acompanhados nos Hemocentros Regionais de Governador Valadares e de Uberaba da Fundação Hemominas. Um grupo conrole constituído de 40 crianças sem DF com média de idade de 12,98 anos também foi incluído para comparações com dados lipídicos. Foram realizadas coletas de dados em registros médicos, exames bioquímicos, genotipagens dos SNPs de ANGPTL4, APOA5, ZNF259 e TNFA, pesquisa de alfa-talassemia e avaliação do uso de hidroxiuréia (HU). Verificaram-se associações entre as variáveis investigadas e, destas, com a ocorrência de eventos clínicos da DF. Para estes fins foram aplicados testes qui-quadrado, Mann-Withiney, Teste T de Students, ANOVA, Kruskal-Wallis e realizadas correlações com o teste de Spearman. A significância estatística foi estabelecida em P < 0,05. Dentre os achados, foram encontrados piores índices de marcadores de hemólise e inflamação nos indivíduos HbSS em relação aos HbSC. A hipocolesterolemia (HDL < 40 mg/dL) foi encontrada em 64,52% da população com DF, havendo diferença significativa entre os indivíduos e os controles, sem diferença entre HbSS e HbSC. Indivíduos com DF que possuíam a HDL superior a 40 mg/dL apresentaram maiores níveis de APOA1 e menores de colesterol total e triglicerídios. A hipertrigliceridemia (TG > 100 mg/dL até os 10 anos e > 130 mg/dL acima de 10 anos) presente em apenas 8,51% dos pacientes DF não mostrou diferença significativa entre os grupos HbSS e HbSC e foi associada com níveis elevados da enzima LDH. Nos indivíduos HbSS os baixos níveis de HDL estavam em maior proporção se comparados ao grupo HbSC. O uso de HU no grupo HbSS não interferiu nos níveis de lipídios. A variante rara do gene ANGPTL4 rs116843064 (G>A), no modelo de dominância, foi associada com redução de leucócitos globais e monócitos e aumento de apolipoproteína A1 e colesterol total nos indivíduos com DF. O polimorfismo de ZNF259 rs964184 (c.724C>G) foi associado ao aumento dos marcadores de hemólise/inflamação (leucócitos globais, reticulócitos e bilirrubinas total e direta) e apresentou efeito dose dependente nos níveis de bilirrubina direta. A variante de menor frequência (-308A) de TNFA rs1800629 foi associada com aumento de 73% dos níveis de bilirrubina direta. A co-herança de alfa-talassemia presente nos dois grupos HbSS e HbSC, reduziu VCM e HCM, mas não influenciou os níveis de HbF, reticulócitos, bilirrubina ou o perfil lipídico. Em conclusão, a hipocolesterolemia foi caracterizada por baixos níveis de HDL em ambos os grupos de indivíduos HbSS e HbSC e o uso terapêutico da hidroxiuréia ou a co-existência de alelos de deleção dos genes HBA parecem não influenciar este quadro dislipidêmico. Entre os polimofismos estudados o de ZNF259 rs964184 foi o único associado a níveis de lipídios nos indivíduos com DF. Nosso estudo é o primeiro a mostrar que a variantes de menor frequência de ZNF259 rs964184 e TNFA rs1800629 estão associadas a hiperbilirrubinemia em pacientes com DF. Hypocholesterolemia and hypertriglyceridemia have been documented in sickle cell disease (SCD) for many years, but the causes and effects on pathophysiology still need to be clarified. In addition, reports on genetic markers related to lipid metabolism that explain the variation of lipid levels and their associations with subtypes of hemolysis and vaso-occlusion and clinical variability of SCD have not been published to date. The overall objective of the study was to investigate whether dyslipidemia and single nucleotide polymorphisms (SNPs) in genes linked to lipid and inflammatory changes would be associated with changes in hematological, biochemical and clinical variables in children and adolescents with the two most frequent forms of SCD, sickle cell anemia (HbSS) and hemoglobinopathy SC (HbSC). The population consisted of 155 individuals born between 2001 and 2010, with a mean age of 12.54 years, being 55.5% male, followed in the Regional Hemocenters of Governador Valadares and Uberaba of the Hemominas Foundation. A conrole group consisting of 40 children without SCD with a mean age of 12.98 years was also included for comparison with lipid data. Data collection on medical records, biochemical tests, genotyping of ANGPTL4, APOA5, ZNF259 and TNFASNPs, alpha-thalassemia screening and assessment of hydroxyurea (HU) use were performed. There were associations between the variables investigated and, of these, with the occurrence of clinical events of the SCD. For these purposes chi-square, Mann-Withiney, Student's T-Test, ANOVA, Kruskal-Wallis and correlations with the Spearman test were applied. Statistical significance was set at P 100 mg / dL up to 10 years and> 130 mg / dL over 10 years) present in only 8.51% of SCD patients showed no significant difference between the HbSS and HbSC groups and was associated with high levels of the LDH enzyme. In the HbSS subjects the low HDL levels were in a higher proportion when compared to the HbSC group. The use of HU in the HbSS group did not interfere with lipid levels. The rare variant of the ANGPTL4 gene rs116843064 (G> A) in the dominance model was associated with reduction of global leukocytes and monocytes and increase of apolipoprotein A1 and total cholesterol in subjects with DF. The polymorphism of ZNF259 rs964184 (c.724C> G) was associated with increased markers of hemolysis/ inflammation (total leukocytes, reticulocytes and total and direct bilirubin) and had a dose-dependent effect on direct bilirubin levels. The lower frequency variant (-308A) of TNFA rs1800629 was associated with a 73% increase in direct bilirubin levels. Alpha-thalassemia co-inheritance in both HbSS and HbSC groups reduced MCV andMCH, but did not influence HbF, reticulocyte, bilirubin or lipid profile levels.In conclusion, hypocholesterolemia was characterized by low levels of HDL in both groups of HbSS and HbSC and the therapeutic use of hydroxyurea or the coexistence of deletion alleles of HBA genes does not appear to influence this dyslipidemic condition. Among the polymorphisms studied, that of ZNF259 rs964184 was the only one associated with lipid levels in SCD. Our study is the first to show that the lower frequency variants of ZNF259 rs964184 and TNFA rs1800629 are associated with hyperbilirubinemia in SCD.