PAULO CALEB JUNIOR DE LIMA SANTOS

(Fonte: Lattes)
Índice h a partir de 2011
21
Lattes
ResearcherID
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina

Filtros

Limpar filtros

Configurações

Autor: PEREIRA, Alexandre Costa ×

Resultados de Busca

Agora exibindo 1 - 10 de 25
  • article 24 Citação(ões) na Scopus
    CYP2C9 and VKORC1 Polymorphisms Are Differently Distributed in the Brazilian Population According to Self-Declared Ethnicity or Genetic Ancestry
    (2012) SOARES, Renata Alonso Gadi; SANTOS, Paulo Caleb Junior Lima; MACHADO-COELHO, George Luiz Lins; NASCIMENTO, Raimundo Marques do; MILL, Jose Geraldo; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa
    Background: Warfarin-dosing pharmacogenetic algorithms have presented different performances across ethnicities, and the impact in admixed populations is not fully known. Aims: To evaluate the CYP2C9 and VKORC1 polymorphisms and warfarin-predicted metabolic phenotypes according to both self-declared ethnicity and genetic ancestry in a Brazilian general population plus Amerindian groups. Methods: Two hundred twenty-two Amerindians (Tupinikin and Guarani) were enrolled and 1038 individuals from the Brazilian general population who were self-declared as White, Intermediate (Brown, Pardo in Portuguese), or Black. Samples of 274 Brazilian subjects from Sao Paulo were analyzed for genetic ancestry using an Affymetrix 6.0 (R) genotyping platform. The CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 g.-1639G>A (rs9923231) polymorphisms were genotyped in all studied individuals. Results: The allelic frequency for the VKORC1 polymorphism was differently distributed according to self-declared ethnicity: White (50.5%), Intermediate (46.0%), Black (39.3%), Tupinikin (40.1%), and Guarani (37.3%) (p < 0.001), respectively. The frequency of intermediate plus poor metabolizers (IM + PM) was higher in White (28.3%) than in Intermediate (22.7%), Black (20.5%), Tupinikin (12.9%), and Guarani (5.3%), (p < 0.001). For the samples with determined ancestry, subjects carrying the GG genotype for the VKORC1 had higher African ancestry and lower European ancestry (0.14 +/- 0.02 and 0.62 +/- 0.02) than in subjects carrying AA (0.05 +/- 0.01 and 0.73 +/- 0.03) (p = 0.009 and 0.03, respectively). Subjects classified as IM + PM had lower African ancestry (0.08 +/- 0.01) than extensive metabolizers (0.12 +/- 0.01) (p = 0.02). Conclusions: The CYP2C9 and VKORC1 polymorphisms are differently distributed according to self-declared ethnicity or genetic ancestry in the Brazilian general population plus Amerindians. This information is an initial step toward clinical pharmacogenetic implementation, and it could be very useful in strategic planning aiming at an individual therapeutic approach and an adverse drug effect profile prediction in an admixed population.
  • article 17 Citação(ões) na Scopus
    Genotyping of the hemochromatosis HFE p.H63D and p.C282Y mutations by high-resolution melting with the Rotor-Gene 6000 (R) instrument
    (2011) SANTOS, Paulo Caleb Junior Lima; SOARES, Renata Alonso Gadi; KRIEGER, Jose Eduardo; GUERRA-SHINOHARA, Elvira Maria; PEREIRA, Alexandre Costa
    Background: The genotyping of HFE p.C282Y and p.H63D mutations is one of the most requested molecular analyses in the laboratorial routine. In this scenario, the main aim was to develop a genotyping assay that has advantages compared to other methods. Methods: Genotypes for the HFE p.C282Y (c.G845A; rs1800562) and p.H63D (c.C187G, rs1799945) mutations were assessed by polymerase chain reaction (PCR) followed by high resolution melting (HRM) analysis with the Rotor-Gene 6000 (R) instrument. Validation studies were conducted in samples bi-directionally sequenced. Results: The melting assay was developed in a unique procedure and to ensure the result in approximately 112 min (31 min for sample preparation and 81 min for the PCR-HRM step). Genotypes for the HFE p.C282Y mutation were easily distinguished in the region of 80-86 degrees C. For the HFE p.H63D, genotypes were also easily distinguished in the region of 76-82 degrees C, but using the addition of known wildtype genotype DNA in all unknown samples plus a reaction without addition. In validation, genotypes were 100% concordant between methods. Conclusions: Our genotyping assay with the Rotor-Gene 6000 (R) instrument applies to the laboratorial routine with several advantages, especially in large-scale demand. The main advantages were the non-dependence on gel electrophoresis and on mutagenic reagents for visualization of fragments, reduction of the chances for contamination due to sample preparation, the lack of use of probe-based methods and cost-effectiveness.
  • article 30 Citação(ões) na Scopus
    Non-HFE hemochromatosis
    (2012) SANTOS, Paulo Caleb Júnior de Lima; DINARDO, Carla Luana; CANÇADO, Rodolfo Delfini; SCHETTERT, Isolmar Tadeu; KRIEGER, José Eduardo; PEREIRA, Alexandre Costa
    Hereditary 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.
  • article 42 Citação(ões) na Scopus
    Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population
    (2013) ALVIM, Rafael de Oliveira; SANTOS, Paulo Caleb Junior Lima; MUSSO, Mariane Manso; CUNHA, Roberto de Sa; KRIEGER, Jose Eduardo; MILL, Jose Geraldo; PEREIRA, Alexandre Costa
    Background: Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods: A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV >= 12 m/s. Results: In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions: These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.
  • article 16 Citação(ões) na Scopus
    Age is associated with time in therapeutic range for warfarin therapy in patients with atrial fibrillation
    (2016) MARCATTO, Leiliane Rodrigues; SACILOTTO, Luciana; DARRIEUX, Francisco Carlos da Costa; HACHUL, Denise Tessariol; SCANAVACCA, Mauricio Ibrahim; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; SANTOS, Paulo Caleb Junior Lima
    Background: Warfarin is the most prescribed oral anticoagulant used for preventing stroke in patients with atrial fibrillation. Time in the therapeutic range (TTR) has been accepted as the best method to evaluate the quality of warfarin therapy. The main aim of the present study was to evaluate the impact of variables on the time in the therapeutic range for warfarin therapy in patients with atrial fibrillation from a referral cardiovascular hospital. Methods: This retrospective study included 443 patients were included (190 patients with age < 65 years and 253 patients with age >= 65 years) from 2011 to 2014 and TTR was computed according to Rosendaal's method. Results: Patients with age >= 65 years had higher TTR value (67+/-22%) compared with patients with < 65 years (60+/-24%) (p = 0.004). In a linear regression model, only age >= 65 years emerged as a significant predictor of greater TTR values. In multivariate logistic regression model, the variable age = 65 years was associated with higher OR for having a TTR higher than the median value (OR = 2.17, p < 0.001). Conclusion: We suggest that the age influenced TTR through greater drug adherence. Strategies for increasing drug adherence might improve quality of warfarin anticoagulation.
  • article 53 Citação(ões) na Scopus
    Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia
    (2014) SANTOS, Paulo Caleb Junior Lima; MORGAN, Aline Cruz; JANNES, Cintia Elin; TUROLLA, Luciana; KRIEGER, Jose Eduardo; SANTOS, Raul D.; PEREIRA, Alexandre Costa
    Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused mainly by LDLR mutations. This study assessed the influence of the presence and type of LDLR mutation on lipid profile and the response to lipid-lowering therapy in Brazilian patients with heterozygous FH. Methods: For 14 +/- 3 months, 156 patients with heterozygous FH receiving atorvastatin were followed. Coding sequences of the LDLR gene were bidirectionally sequenced, and the type of LDLR mutations were classified according to their probable functional class. Results: The frequencies of the types of LDLR mutations were: null-mutation (n = 40, 25.6%), defective-mutation (n = 59, 37.8%), and without an identified mutation (n = 57, 36.6%). Baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were higher in patients carrying a null mutation (9.9 +/- 1.9 mmol/L, 7.9 +/- 1.7 mmol/L), compared to those with a defective (8.9 +/- 2.2 mmol/L, 7.0 +/- 2.0 mmol/L), or no mutation (7.9 +/- 1.9 mmol/L, 5.8 +/- 1.9 mmol/L) (p < 0.001). After treatment, the proportion of patients attaining an LDL-C<3.4 mmol/L was significantly different among groups: null (22.5%), defective (27.1%), and without mutations (47.4%) (p = 0.02). The presence of LDLR mutations was independently associated with higher odds of not achieving the LDL-C cut-off (OR 9.07, 95% CI 1.41-58.16, p = 0.02). Conclusions: Our findings indicate that the presence and type of LDLR mutations influence lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous FH. Thus, more intensive care with pharmacological therapeutics should be performed in patients who have a molecular analysis indicating the presence of a LDLR mutation. (C) 2014 Published by Elsevier Ireland Ltd.
  • article 54 Citação(ões) na Scopus
    Ethnicity and Arterial Stiffness in Brazil
    (2011) SANTOS, Paulo Caleb Junior de Lima; ALVIM, Rafael de Oliveira; FERREIRA, Noely Evangelista; CUNHA, Roberto de Sa; KRIEGER, Jose Eduardo; MILL, Jose Geraldo; PEREIRA, Alexandre Costa
    BACKGROUND The impact of increased central arterial stiffness as a predictor of morbidity and mortality, independently of other cardiovascular (CV) risk factors, has been established. The main aim of the present work was to investigate the association of ethnicity on arterial stiffness in different ethnic groups from the Brazilian population. METHODS A total of 1,427 individuals from the general population were randomly selected from the Vitoria City metropolitan area and 588 Amerindians from a native community in Brazil. The ethnicity of the general population was classified by a standard questionnaire as Caucasian descent, African descent, or Mulattos (considered racially mixed subjects). Pulse wave velocity (PWV) was measured with a noninvasive automatic device (Complior, Colson; Garges les Gonesses, France). RESULTS Hemodynamic data of PWV, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was higher in African descent individuals than in the other groups (P < 0.001). These results were still observed after adjustment for age and mean arterial pressure (P < 0.001). In addition, studying only normotensive individuals, PWV adjusted levels were higher in African descent individuals, and lower in Amerindians when compared with other ethnic groups (P < 0.01), showing, without the possible confounder effects of time and severity of hypertension or medication use, that PWV is associated with ethnicity in our population. CONCLUSION The study of different ethnic groups from a highly admixtured population was able to demonstrate an association between ethnicity and arterial stiffness.
  • article 7 Citação(ões) na Scopus
    Influence of smoking cessation drugs on blood pressure and heart rate in patients with cardiovascular disease or high risk score: real life setting
    (2016) SILVA, Andre Pacheco; SCHOLZ, Jaqueline; ABE, Tania Ogawa; PINHEIRO, Gabriela Gouveia; GAYA, Patricia Viviane; PEREIRA, Alexandre Costa; SANTOS, Paulo Caleb Junior Lima
    Background: Smoking is the most important reversible cardiovascular risk factor. It is well established that quitting smoking reduces coronary events. However, on several occasions, the cardiovascular safety of smoking cessation drugs has been questioned. Our goal is to evaluate the effects of smoking cessation drugs on blood pressure and heart rate in patients from a smoking cessation service in a cardiology hospital. Methods: We examined the PAF database (Smoking Cessation Assistance Program database) between January 2008 and March 2014. We analyzed data from 900 patients who were compliant with the treatment (50.5 % male, average age 53 +/- 17 years). The most frequent clinical diagnoses were coronary artery disease (25.2 %), hypertension (57.2 %), and diabetes (13.4 %). Blood pressure, heart rate, and carbon monoxide (CO) concentration in exhaled air were analyzed at consecutive visits during the first 45 days of treatment (mean visits - 3). Analysis of repeated measures was used for the statistical analysis (p < 0.05). Results: Two hundred seventy one patients used nicotine replacement therapy (NRT) alone, 81 used bupropion alone, 154 used varenicline alone, 283 used NRT plus bupropion and 111 used bupropion plus varenicline. For all smoking cessation drugs, used alone or in combination, no increase occurred in the average value of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). Significant reductions in CO concentrations occurred in all smoking cessation drug groups. Conclusion: Smoking cessation drugs used in monotherapy or in combined regimens did not influence systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in this group of patients during the observation period.
  • article 7 Citação(ões) na Scopus
    Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial
    (2016) MARCATTO, Leiliane Rodrigues; SACILOTTO, Luciana; BUENO, Carolina Tosin; FACIN, Mirella; STRUNZ, Celia Maria Cassaro; DARRIEUX, Francisco Carlos Costa; SCANAVACCA, Mauricio Ibrahim; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; SANTOS, Paulo Caleb Junior Lima
    Background: Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (<50%) are associated with greater risk of thromboembolic and bleeding events. Recently, we developed a pharmacogenetic-based warfarin dosing algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (<50%) from a tertiary cardiovascular hospital. Methods/design: This study is a randomized controlled trial in patients (n = 300) with atrial fibrillation with TTR <50%, based on the last three INR values. At the first consultation, patients will be randomized into two groups: TA group (traditional anticoagulation) and PA group (pharmacogenetic anticoagulation). For the first group, the physician will adjust the dose according to current INR value and, for the second group, a pharmacogenetic algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient's INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of Sao Paulo Medical School. Discussion: This randomized study will include patients with low TTR and it will evaluate whether a population-specific genetic algorithm might be more effective than traditional anticoagulation for a selected group of poorly anticoagulated patients.
  • article 35 Citação(ões) na Scopus
    Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration
    (2015) SANTOS, Paulo Caleb Junior Lima; MARCATTO, Leiliane Rodrigues; DUARTE, Nubia Esteban; SOARES, Renata Alonso Gadi; STRUNZ, Celia Maria Cassaro; SCANAVACCA, Maurcio; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa
    Background: The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population. Materials & methods: We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133). Results: Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms. Conclusion: Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available.