PAULO CALEB JUNIOR DE LIMA SANTOS
Projetos de Pesquisa
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LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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- 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 CostaObjectives: 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.
conferenceObject COST EFFECTIVENESS ANALYSIS OF VARENICLINE USE FOR SMOKING CESSATION IN THE CITY OF SAO PAULO FROM THE PUBLIC HEALTH SYSTEM PERSPECTIVE(2014) PORTELA, L. D.; ISSA, J. S.; SANTOS, V. G.; SANTOS, P. C. J. D. L.; PEREIRA, A. D. C.; CIPRIANO, S. L.; FERREIRA, C. N.; MANFRIN, D. F.conferenceObject ACTN3 R577X polymorphism and long-term survival in patients with chronic heart failure(2014) BERNARDEZ, S.; SANTOS, P. C. J. L.; KRIEGER, J. E.; MANSUR, A. J.; PEREIRA, A. C.- MYH9 and APOL1 Gene Polymorphisms and the Risk of CKD in Patients with Lupus Nephritis from an Admixture Population(2014) COLARES, Vinicius Sardao; TITAN, Silvia Maria de Oliveira; PEREIRA, Alexandre da Costa; MALAFRONTE, Patricia; CARDENA, Mari M.; SANTOS, Sidney; SANTOS, Paulo C.; FRIDMAN, Cintia; BARROS, Rui Toledo; WORONIK, ViktoriaMYH9 polymorphisms have been described to be associated with the risk of CKD in non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black descendants, MHY9 genetic variants could partially explain the excess risk of CKD associated with African ancestry. However, recent data suggests that APOL1 gene co-segregate with MYH9, and could be the gene truly associated with CKD risk. In this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3 rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD). Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9 polymorphism showed a positive association (HR3.72, 95% CI 1.47-9.38, p = 0.005). When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present in 29.7% in the PO group vs. 18.5% in controls) showed a significant association to the risk of PO, even after adjustments for baseline estimated creatinine clearance and autossomal ancestry (HR 2.0, 95% CI 1.2-3.4, p = 0.01). Our results show that in our population MYH9, but not APOL1, gene polymorphisms confer an increased risk of CKD in LN patients, independently of race.
- LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography(2014) SANTOS, Paulo C. J. L.; BUENO, Carolina T.; LEMOS, Pedro A.; KRIEGER, Jose E.; PEREIRA, Alexandre C.Background: Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients. Methods: 1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis. Results: The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95% CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95% CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes. Conclusions: We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association.
article 20 Citação(ões) na Scopus Simultaneous Use of Amiodarone Influences Warfarin Maintenance Dose but Is Not Associated with Adverse Events(2014) SANTOS, Paulo Caleb Junior Lima; SOARES, Renata Alonso Gadi; STRUNZ, Celia Maria Cassaro; GRINBERG, Max; FERREIRA, Joao Fernando M. .; CESAR, Luiz Antonio Machado; SCANAVACCA, Mauricio; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaBACKGROUND: Drug interaction studies selecting patients in a real-life setting are scarce, and most studies to date are characterized by a small sample size. OBJECTIVE: To evaluate the effect of amiodarone on warfarin maintenance dose and adverse events in an anticoagulation cohort from a tertiary cardiovascular service. METHODS: This study recruited 866 patients, and oral anticoagulant therapy was monitored by the prothrombin time expressed as the international normalized ratio (INR). Genotyping of CYP2C9*2, CYP2C9*3, and VKORC1 3673 polymorphisms was performed. RESULTS: Of the 866 patients, 111 (12.8%) were taking amiodarone and warfarin simultaneously, and 514 (59.4%) reached the therapeutic target dose. The warfarin maintenance dose was significantly lower in patients simultaneously using amiodarone (23.8 +/- 11.3 mg/wk) compared with other patients (29.5 +/- 14.3 mg/wk; P < 0.001). Patients taking amiodarone had higher INR/current dose ratios (0.83 +/- 0.04 per mg) compared with patients not using amiodarone (0.71 +/- 0.02 per mg, P = 0.001). Adverse event frequency was not different between the groups (P = 0.40). No genotype effect was noted on the odds of bleeding associated with amiodarone use. CONCLUSIONS: Simultaneous use of amiodarone influences warfarin maintenance dose, but is not associated with adverse events.conferenceObject Hemodynamic characteristics by impedance cardiography according to different etiologies in chronic heart failure - GENIUS-HF substudy(2014) BERNARDEZ, SSabrina; GIOLI-PEREIRA, L.; MARCONDES-BRAGA, F. G.; SPINA, J. M. R.; SANTOS, P. C. J. L.; BACAL, F.; MANSUR, A. J.; MESQUITA, E. T.; KRIEGER, J. E.; PEREIRA, A. C.- ACTN3 R577X polymorphism and long-term survival in patients with chronic heart failure(2014) BERNARDEZ-PEREIRA, Sabrina; SANTOS, Paulo Caleb Junior Lima; KRIEGER, Jose Eduardo; MANSUR, Alfredo Jose; PEREIRA, Alexandre CostaBackground: Previous studies have shown the occurrence of actinin-3 deficiency in the presence of the R577X polymorphism in the ACTN3 gene. Our hypothesis is that this deficiency, by interfering with the function of skeletal muscle fiber, can result in a worse prognosis in patients with chronic heart failure. Methods: A prospective cohort study was conducted from 2002 to 2004. The eligibility criteria included diagnosis of chronic heart failure stage C from different etiologies. We excluded all patients with concomitant disease that could be related to poor prognosis. ACTN3 rs1815739 (R577X) polymorphism was detected by high resolution melting analysis. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between the baseline variables and the composite end-point of all-cause death was assessed using a Cox proportional hazards survival model. Results: A total of 463 patients were included in this study. The frequency of the ACTN3 577X variant allele was 39.0%. The LVEF mean was 45.6 +/- 18.7% and the most common etiology of this study was hypertensive. After a follow-up of five years, 239 (51.6%) patients met the pre-defined endpoint. Survival curves showed higher mortality in patients carrying RX or XX genotypes compared with patients carrying RR genotype (p = 0.01). Conclusion: R577X polymorphism in the ACTN3 gene was independently associated with worse survival in patients with chronic heart failure. Further studies are necessary to ensure its use as a marker of prognosis for this syndrome.
- Smoking cessation and weight gain in patients with cardiovascular disease or risk factor(2014) ISSA, Jaqueline S.; SANTOS, Paulo C. J. L.; VIEIRA, Lis P.; ABE, Tania O.; KUPERSZMIDT, Carla S.; NAKASATO, Miyoko; CARDOSO, Elisabeth; AMORIM, Clarice; PEREIRA, Alexandre C.