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Made available in DSpace on 2014-12-02T11:16:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-24Bitstream added on 2014-12-02T11:21:27Z : No. of bitstreams: 1 000799353_20160224.pdf: 289799 bytes, checksum: 0b2547aa37c5af1df5323abf3c3ac04e (MD5) Bitstreams deleted on 2016-02-24T11:27:50Z: 000799353_20160224.pdf,. Added 1 bitstream(s) on 2016-02-24T11:28:33Z : No. of bitstreams: 1 000799353.pdf: 4598958 bytes, checksum: c90c43cb77dd0d3eaea210da3979de05 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) A doença falciforme (DF) é caracterizada por heterogeneidade clínica variando de pessoas com relativamente poucas complicações clínicas e expectativa de vida normal, até aqueles com complicações graves, como hipertensão pulmonar, priapismo, acidente vascular cerebral (AVC), úlceras de perna, episódios de dor, síndrome torácica aguda (STA) e osteonecrose. O tratamento com a hidroxiureia (HU) tem conquistado espaço na terapia adotada pelos clínicos e sua experiência na DF vem sendo acumulada ao longo dos últimos 25 anos. Porém, muitos estudos têm sido elaborados para investigar as variações genéticas que possam explicar o porquê de alguns pacientes tolerarem e respondem ao uso de HU, enquanto, outros ainda precisam ser tratados por terapias alternativas. Diante disso, nosso objetivo foi avaliar a resposta ao tratamento com a HU considerando a influência dos polimorfismos genéticos envolvidos na fisiopatologia da DF. Para isso, usamos a calculadora de gravidade da DF (CGDF); rastreamos os polimorfismos -509C/T (TGFB1), -308G/A (TNFA), 313 A/G (GSTP1), -786T/C (NOS3), nulos (GSTM1 e GSTT1); e avaliamos os marcadores de estresse oxidativo (catalase, glutationa peroxidase-GPx, glutationa S-transferase-GST, glutationa redutase-GR e as espécies reativas ao ácido tiobarbitúrico-TBARS). O estudo envolveu 520 pacientes, acima de cinco anos de idade, provenientes do Instituto de Hematologia do Rio de Janeiro/RJ-HEMORIO. A CGDF foi validada para os pacientes brasileiros e os escores de gravidade foram relacionados com os marcadores de estresse oxidativo. Em relação aos polimorfismos, a presença do alelo nulo do gene GSTM1 aumentou a chance de ocorrência de priapismo em pacientes com a DF. A mutação do gene TGFB1 mostrou efeito protetor na ocorrência de STA e úlceras de perna, e à presença do alelo mutante para o gene NOS3 diminuiu a chance de ocorrência de retinopatia e priapismo. Para os marcadores bioquímicos, ... Sickle cell disease (SCD) is characterized by a very heterogeneous clinical ranging from patients who have normal life expectancy with relatively few complications; others can have severe complications such as pulmonary hypertension, priapism, stroke, leg ulceration, recurrent painful episodes, acute chest syndrome (ACS) and avascular necrosis of bone (AVN). Treatment with hydroxyurea (HU) has become more adopted by medical and HU experience in DF has been accumulated over the last 25 years. However, many studies have been designed to investigate the genetic variations that may explain why some patients tolerate and respond to the use of HU, while others still need to be treated with alternative therapies. In view of this, we aimed to evaluate the response to HU treatment considering the genetic polymorphisms influence involved in the pathophysiology of SCD. For this, we used the calculator severity of DF (CGDF); detected the polymorphisms -509C/T (TGFB1), -308G/A (TNFA), 313 A/G (GSTP1), -786T/C (NOS3), null (GSTM1 and GSTT1), we assessed markers of oxidative stress (catalase, glutathione peroxidase-GPx, glutathione S-transferase-GST, glutathione reductase-GR and the thiobarbituric acid reactive species-TBARS). The study involved 520 patients older than 5 years, from the Instituto de Hematologia do Rio de Janeiro/RJ-HEMORIO. The CGDF was validated for Brazilian patients and severity scores were related to oxidative stress markers. The presence of the GSTM1 null allele increased the occurrence chance of priapism in SCD patients. TGFB1 gene mutation had a protective effect on the occurrence of STA and leg ulcers, and the presence of the mutant allele for the NOS3 gene decreased the occurrence chance of retinopathy and priapism. For biochemical markers, we found that the decreased of enzymes activity (catalase, Gpx and GR), and the increased in GST activity were associated with greater SCD severity. In addition, lipid peroxidation levels ...