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
- Mitochondrial and genomic ancestry are associated with etiology of heart failure in Brazilian patients(2016) CARDENA, M. M. S. G.; RIBEIRO-DOS-SANTOS, A. K.; SANTOS, S. E. B.; MANSUR, A. J.; BERNARDEZ-PEREIRA, S.; SANTOS, P. C. J. L.; PEREIRA, A. C.; FRIDMAN, C.There is a high prevalence of heart failure (HF) in the general population, but it is more common in black people. We evaluated the association between genomic ancestry and mitochondrial haplogroups (mt-haplogroups) with HF etiology in 503 Brazilian patients. We elicited Mt-haplogroups by analyzing the control region of mitochondrial DNA, and genomic ancestry, by using 48 autosomal insertiondeletion ancestry informative markers. Hypertensive (28.6%, n = 144) and ischemic (28.4%, n = 143) etiologies of HF were the most prevalent herein. Our results showed that 233 individuals (46.3%) presented African mitochondrial (mt)-haplogroups, and the major contribution in the genomic ancestry analysis was the European ancestry (57.5% (+/- 22.1%)). African mt-haplogroups were positively associated with a diagnosis of hypertensive cardiomyopathy (odds ratio, OR 1.55, confidence interval, CI 95% 1.04-2.44, P = 0.04) when compared with European mt-haplogroups. Regarding the genomic ancestry, the African ancestry variant had higher risks (OR 7.84, 95% CI 2.81-21.91, P < 0.001), whereas the European ancestry variant had lower risks (OR 0.14, 95% CI 0.04-5.00, P < 0.001) for developing the hypertensive etiology. In addition, European ancestry showed an OR of 4.05 (CI 95% 1.53-10.74, P = 0.005), whereas African ancestry showed an OR of 0.17 (CI 95% 0.06-0.48, P = 0.001) for developing ischemic etiology. In conclusion, this study supports the importance of using ancestry informative markers and mitochondrial DNA to study the genetics of complex diseases in admixed populations to improve the management, treatment and prevention of these illnesses. Therefore, the ancestry informative markers and mt-haplogroups could provide new biomarkers to be associated with HF etiologies and be used as a premise for more specific management.
- Genomic ancestry as a predictor of haemodynamic profile in heart failure(2016) BERNARDEZ-PEREIRA, Sabrina; GIOLI-PEREIRA, Luciana; MARCONDES-BRAGA, Fabiana G.; SANTOS, Paulo Caleb Junior Lima; SPINA, Joceli Mabel Rocha; HORIMOTO, Andrea Roseli Vancan Russo; SANTOS, Hadassa Campos; BACAL, Fernando; FERNANDES, Fabio; MANSUR, Alfredo Jose; PIETROBON, Ricardo; KRIEGER, Jose Eduardo; MESQUITA, Evandro Tinoco; PEREIRA, Alexandre CostaObjective: The aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF). Methods: Observational, cross-sectional study. Eligible participants were aged between 18 and 80 years; ejection fraction was <= 50%. Patients underwent genetic analysis of ancestry informative markers, echocardiography and impedance cardiography (ICG). Race was determined by self-classification into two groups: white and non-white. Genomic ancestry was estimated using a panel of 101 348 polymorphic markers and three continental reference populations (European, African and Native American). Results: Our study included 362 patients with HF between August 2012 and August 2014. 123 patients with HF declared themselves as white and 234 patients declared themselves as non-white. No statistically significant differences were found regarding the ICG parameters according to self-declared race. The Amerindian ancestry was positively correlated with systolic time ratio (r=0.109, p<0.05). The thoracic fluid content index (r=0.124. p<0.05), E wave peak (r=0.127. p<0.05) and E/e' ratio (r=0.197. p<0.01) were correlated positively with African ancestry. In multiple linear regression, African ancestry remained associated with the E/e0 ratio, even after adjustment to risk factors. Conclusions: The African genetic ancestry was associated with worse parameters of diastolic function; the Amerindian ancestry correlated with a worse pattern of ventricular contractility, while self-declared colour was not helpful to infer haemodynamic profiles in HF.
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.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.