PAULO CALEB JUNIOR DE LIMA SANTOS
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Non-HFE hemochromatosis(2012) SANTOS, Paulo Caleb Júnior de Lima; DINARDO, Carla Luana; CANÇADO, Rodolfo Delfini; SCHETTERT, Isolmar Tadeu; KRIEGER, José Eduardo; PEREIRA, Alexandre CostaHereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. Nowadays, four main genes are implicated in the pathophysiology of clinical syndromes classified as non-HFE hemochromatosis: hemojuvelin (HJV, type 2Ajuvenile HH), hepcidin (HAMP, type 2B juvenile HH), transferrin receptor 2 (TFR2, type 3 HH) and ferroportin (SLC40A1, type 4 HH). The aim of this review is to explore molecular, clinical and management aspects of non-HFE hemochromatosis.
bookPart Fármacos utilizados no tratamento de anemias(2021) ALVARENGA, Aline Morgan; DINARDO, Carla Luana; SANTOS, Paulo Caleb Júnior de Lima- Two new mutations in the HIF2A gene associated with erythrocytosis(2012) PERCY, Melanie J.; CHUNG, Yu Jin; HARRISON, Claire; MERCIECA, Jane; HOFFBRAND, A. Victor; DINARDO, Carla L.; SANTOS, Paulo C. J. L.; FONSECA, Guilherme H. H.; GUALANDRO, Sandra F. M.; PEREIRA, Alexandre C.; LAPPIN, Terence R. J.; MCMULLIN, Mary Frances; LEE, Frank S.Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen-sensing pathway that regulates the Erythropoietin (EPO) gene. More specifically, recent studies have identified erythrocytosis-associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor-2 alpha (HIF-2 alpha), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met-535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe-540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF-2 alpha with both VHL and PHD2.
- CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation(2013) SANTOS, Paulo Caleb Junior Lima; DINARDO, Carla Luana; SCHETTERT, Isolmar Tadeu; SOARES, Renata Alonso Gadi; KAWABATA-YOSHIHARA, Liz; BENSENOR, Isabela Martins; KRIEGER, Jose Eduardo; LOTUFO, Paulo Andrade; PEREIRA, Alexandre CostaThe main aim of this study was to determine whether CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability during initial dose-finding phase and during maintenance treatment after 360 days. Two hundred and six consecutive patients who were beginning warfarin therapy were selected. They were assessed for general and clinical characteristics; prescribed warfarin dose; response to therapy on days 7-10, 30, 60, 180, and 360; adverse events; and CYP2C9 *2, *3, *5, *6, *8, *11, and VKORC1 1639G > A assays. During the first 30 days of anticoagulation, the relative variability of warfarin dose was significantly associated with CYP2C9*2 and CYP2C9*3 polymorphisms (p = 0.02) and with VKORC1 1639G > A genotypes (p = 0.04). Warfarin variability was also statistically different according to predicted metabolic phenotype and to VKORC1 genotypes after 360 days of treatment, and in the phase between 180 and 360 days (long-term dose variability). Both CYP2C9 and VKORC1 polymorphisms were associated with the international normalized ratio (INR) made between 7 and 10 days/initial dose ratio, adjusted for covariates (p < 0.01 and p = 0.02, respectively). Patients carrying VKORC1 and CYP2C9 variants presented lower required dose (at the end of follow-up of 360 days) compared to patients carrying wild-type genotypes (p = 0.04 and p = 0.03, respectively). Genetic information on CYP2C9 and VKORC1 is important both for the initial dose-finding phase and during maintenance treatment with warfarin.
- Quality of life scores differs between genotypic groups of patients with suspected hereditary hemochromatosis(2018) FONSECA, Paula Fernanda Silva; CANCADO, Rodolfo Delfini; NAOUM, Flavio Augusto; DINARDO, Carla Luana; FONSECA, Guilherme Henrique Hencklain; GUALANDRO, Sandra Fatima Menosi; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; BRISSOT, Pierre; SANTOS, Paulo Caleb Junior LimaBackground: Hereditary hemochromatosis (HH) encompasses a group of autosomal recessive disorders mainly characterized by enhanced intestinal absorption of iron and its accumulation in parenchymal organs. HH diagnosis is based on iron biochemical and magnetic resonance imaging (MRI) assessment, and genetic testing. Questionnaires, such as SF-36 (short form health survey), have been increasingly used to assess the impact of diseases on the patient's quality of life (QL). In addition, different genotypes are identified as results of genetic tests in patients with suspected primary iron overload. In the present study, our aim was to evaluate whether domains of QL are different according to genotypic groups in patients suspected of HH. Methods: Seventy-nine patients with primary iron overload were included and two genotypic groups were formed (group 1: homozygous genotype for the HFE p.Cys282Tyr mutation; group 2: other genotypes). Results: Group 1 had higher means of plasma transferrin saturation (86 +/- 19%) and serum ferritin (1669 +/- 1209 ng/mL) compared to group 2 (71 +/- 12%, 1252 +/- 750 ng/mL, respectively; p = 0.001). Four domains were significantly different among groups 1 and 2: physical functioning (p = 0.03), bodily pain (p = 0.03), vitality (p = 0.02) and social functioning (p = 0.01). Conclusions: Our main finding was that patients with p. Cys282Tyr homozygosity had a worse QL scenario assessed by SF-36, compared with patients with iron overload without the same genotype. Being aware of this relationship between genotypes and QL might be helpful in the overall management of patients suspected of hereditary hemochromatosis.