HADASSA CAMPOS SANTOS
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Butyrylcholinesterase Genetic Variants: Association with Cocaine Dependence and Related Phenotypes(2013) NEGRAO, Andre Brooking; PEREIRA, Alexandre Costa; GUINDALINI, Camila; SANTOS, Hadassa Campos; MESSAS, Guilherme Peres; LARANJEIRA, Ronaldo; VALLADA, HomeroObjective: The search for genetic vulnerability factors in cocaine dependence has focused on the role that neuroplasticity plays in addiction. However, like many other drugs, the ability of an individual to metabolize cocaine can also influence susceptibility to dependence. Butyrylcholinesterase (BChE) metabolizes cocaine, and genetic variants of the BChE gene (BCHE) alter its catalytic activity. Therefore, we hypothesize that cocaine users with polymorphisms in BCHE can show diverse addictive behaviors due to differences in effective plasma concentrations of cocaine. Those polymorphisms might also influence users to prefer one of the two main preparations (crack or powder cocaine), despite having equal access to both. The present work investigates polymorphisms in BCHE and if those genetic variants constitute risk factors for cocaine dependence and for crack cocaine use. Methods: A total of 1,436 individuals (698 cocaine-dependent patients and 738 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in BCHE: rs1803274, rs4263329, and rs4680662. Results: For rs4263329, a nominal difference was found between cases and controls. For rs1803274 (the functional SNP), a statistically significant difference was found between patients who used crack cocaine exclusively and those who used only powder cocaine (P = 0.027; OR = 4.36; 95% CI = 1.18-16.04). Allele frequencies and genotypes related to other markers did not differ between cases and controls or between the two cocaine subgroups. Conclusions: Our findings suggest that the AA genotype of rs1803274 is a risk factor for crack cocaine use, which is more addictive than powder cocaine use. Further studies are needed in order to confirm this preliminary result and clarify the role of BCHE and its variants in cocaine dependence.
- Smoking and Female Sex: Independent Predictors of Human Vascular Smooth Muscle Cells Stiffening(2015) DINARDO, Carla Luana; SANTOS, Hadassa Campos; VAQUERO, Andre Ramos; MARTELINI, Andre Ricardo; DALLAN, Luis Alberto Oliveira; ALENCAR, Adriano Mesquita; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaAims Recent evidence shows the rigidity of vascular smooth muscle cells (VSMC) contributes to vascular mechanics. Arterial rigidity is an independent cardiovascular risk factor whose associated modifications in VSMC viscoelasticity have never been investigated. This study's objective was to evaluate if the arterial rigidity risk factors aging, African ancestry, female sex, smoking and diabetes mellitus are associated with VMSC stiffening in an experimental model using a human derived vascular smooth muscle primary cell line repository. Methods Eighty patients subjected to coronary artery bypass surgery were enrolled. VSMCs were extracted from internal thoracic artery fragments and mechanically evaluated using Optical Magnetic Twisting Cytometry assay. The obtained mechanical variables were correlated with the clinical variables: age, gender, African ancestry, smoking and diabetes mellitus. Results The mechanical variables Gr, G'r and G""r had a normal distribution, demonstrating an inter-individual variability of VSMC viscoelasticity, which has never been reported before. Female sex and smoking were independently associated with VSMC stiffening: Gr (apparent cell stiffness) p = 0.022 and p = 0.018, R-2 0.164; G'r (elastic modulus) p = 0.019 and p = 0.009, R-2 0.184 and G""r (dissipative modulus) p = 0.011 and p = 0.66, R-2 0.141. Conclusion Female sex and smoking are independent predictors of VSMC stiffening. This pro-rigidity effect represents an important element for understanding the vascular rigidity observed in post-menopausal females and smokers, as well as a potential therapeutic target to be explored in the future. There is a significant inter-individual variation of VSMC viscoelasticity, which is slightly modulated by clinical variables and probably relies on molecular factors.
- Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations(2015) KEHDY, Fernanda S. G.; GOUVEIA, Mateus H.; MACHADO, Moara; MAGALHAES, Wagner C. S.; HORIMOTO, Andrea R.; HORTA, Bernardo L.; MOREIRA, Rennan G.; LEAL, Thiago P.; SCLIAR, Marilia O.; SOARES-SOUZA, Giordano B.; RODRIGUES-SOARES, Fernanda; ARAUJO, Gilderlanio S.; ZAMUDIO, Roxana; ANNA, Hanaisa P. Sant; SANTOS, Hadassa C.; DUARTE, Nubia E.; FIACCONE, Rosemeire L.; FIGUEIREDO, Camila A.; SILVA, Thiago M.; COSTA, Gustavo N. O.; BELEZA, Sandra; BERG, Douglas E.; CABRERA, Lilia; DEBORTOLI, Guilherme; DUARTE, Denise; GHIROTTO, Silvia; GILMAN, Robert H.; GONCALVES, Vanessa F.; MARRERO, Andrea R.; MUNIZ, Yara C.; WEISSENSTEINER, Hansi; YEAGER, Meredith; RODRIGUES, Laura C.; BARRETO, Mauricio L.; LIMA-COSTA, M. Fernanda; PEREIRA, Alexandre C.; RODRIGUES, Maira R.; TARAZONA-SANTOS, EduardoWhile South Americans are underrepresented in human genomicdiversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.
- Increasing The Genetic Admixture of Available Lines of Human Pluripotent Stem Cells(2016) TOFOLI, Fabiano A.; DASSO, Maximiliano; MORATO-MARQUES, Mariana; NUNES, Kelly; PEREIRA, Lucas Assis; SILVA, Giselle Siqueira da; FONSECA, Simone A. S.; COSTAS, Roberta Montero; SANTOS, Hadassa Campos; PEREIRA, Alexandre da Costa; LOTUFO, Paulo A.; BENSENOR, Isabela M.; MEYER, Diogo; PEREIRA, Lygia VeigaHuman pluripotent stem cells (hPSCs) may significantly improve drug development pipeline, serving as an in vitro system for the identification of novel leads, and for testing drug toxicity. Furthermore, these cells may be used to address the issue of differential drug response, a phenomenon greatly influenced by genetic factors. This application depends on the availability of hPSC lines from populations with diverse ancestries. So far, it has been reported that most lines of hPSCs derived worldwide are of European or East Asian ancestries. We have established 23 lines of hPSCs from Brazilian individuals, and we report the analysis of their genomic ancestry. We show that embryo-derived PSCs are mostly of European descent, while induced PSCs derived from participants of a national-wide Brazilian cohort study present high levels of admixed European, African and Native American genomic ancestry. Additionally, we use high density SNP data and estimate local ancestries, particularly those of CYP genes loci. Such information will be of key importance when interpreting variation among cell lines with respect to cellular phenotypes of interest. The availability of genetically admixed lines of hPSCs will be of relevance when setting up future in vitro studies of drug response.