HADASSA CAMPOS 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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- Self-declared ethnicity associated with risk factors of cardiovascular diseases in an urban sample of the Brazilian population: The role of educational status in the association(2013) SANTOS, H. C.; FRAGOSO, T. M.; MACHADO-COELHO, G. L.; NASCIMENTO, R. M. do; MILL, J. G.; KRIEGER, J. E.; PEREIRA, A. C.
- 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.
- A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set(2016) SANTOS, Hadassa C.; HORIMOTO, Andrea V. R.; TARAZONA-SANTOS, Eduardo; RODRIGUES-SOARES, Fernanda; BARRETO, Mauricio L.; HORTA, Bernardo L.; LIMA-COSTA, Maria F.; GOUVEIA, Mateus H.; MACHADO, Moara; SILVA, Thiago M.; SANCHES, Jose M.; ESTEBAN, Nubia; MAGALHAES, Wagner C. S.; RODRIGUES, Maira R.; KEHDY, Fernanda S. G.; PEREIRA, Alexandre C.The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost-and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using similar to 370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals.
- The Duffy null genotype is associated with a lower level of CCL2, leukocytes and neutrophil count but not with the clinical outcome of HTLV-1 infection(2017) SILVA-MALTA, Maria Clara Fernandes da; SALES, Camila Campos; GUIMARAES, Jacqueline Cronemberger; GONCALVES, Poliane de Cassia; CHAVES, Daniel Goncalves; SANTOS, Hadassa Campos; PEREIRA, Alexandre da Costa; RIBAS, Joao Gabriel; CARNEIRO-PROIETTI, Anna Barbara de Freitas; MARTINS, Marina LobatoPurpose. Chemokines are important in the immune response against viral infections, and may play a role in human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis. Polymorphisms in the Duffy antigen receptor for chemokines (DARC), such as rs12075 (A>G; FY*B>FY*A) and rs281477 (46T>C; GATA-1 box) may influence circulating concentrations of proinflammatory chemokines. We investigate whether Duffy genotypes influence the HTLV-1 proviral load (PVL) level, HTLV-1 infection outcome and chemokine concentrations in HTLV-1 asymptomatic carriers (AC=162), HAM/TSP patients (HAM=135) and seronegative individuals (SN=71). Methodology. Quantification of plasmatic IL8, CCL2 and CCL5 were performed by flow cytometry and Duffy genotypes were investigated by real-time PCR. HTLV-1 PVL was quantified in peripheral blood. To control for spurious association, individual ancestry profiles in AC and HAM groups were investigated. Results/Key findings. PVL and IL8 level were significantly higher in the HAM group than in the AC group, but were not associated with Duffy genotypes. The highest CCL2 and CCL5 levels were seen in the SN group, and there was no difference when comparing the infected groups. The level of CCL5 was not associated with Duffy genotypes. The polymorphism 46 C/C that abrogates the DARC expression on the erythrocytes was significantly associated with lower levels of CCL2, neutrophil and white blood cell (WBC) counts in HTLV-1-infected individuals. Conclusion. We conclude that although the Duffy null genotype was associated with leukopenia, neutropenia and lower levels of CCL2, the data do not suggest the influence of Duffy genotypes on the neurologic outcome of HTLV-1 infection, but may be a confounding factor in comparison HTLV-1-infected populations with different ancestries, especially when defining inflammatory biomarkers.
- 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.
- Cohort profile: the Baependi Heart Study - a family-based, highly admixed cohort study in a rural Brazilian town(2016) EGAN, Kieren J.; SCHANTZ, Malcolm von; NEGRAO, Andre B.; SANTOS, Hadassa C.; HORIMOTO, Andrea R. V. R.; DUARTE, Nubia E.; GONCALVES, Guilherme C.; SOLER, Julia M. P.; ANDRADE, Mariza de; LORENZI-FILHO, Geraldo; VALLADA, Homero; TAPOROSKI, Tamara P.; PEDRAZZOLI, Mario; AZAMBUJA, Ana P.; OLIVEIRA, Camila M. de; ALVIM, Rafael O.; KRIEGER, Jose E.; PEREIRA, Alexandre C.Purpose: Cardiovascular disease (CVD) is a major challenge to global health. The same epidemiological transition scenario is replayed as countries develop, but with variations based on environment, culture and ethnic mixture. The Baependi Heart Study was set up in 2005 to develop a longitudinal family-based cohort study that reflects on some of the genetic and lifestyle-related peculiarities of the Brazilian populations, in order to evaluate genetic and environmental influences on CVD risk factor traits. Participants: Probands were recruited in Baependi, a small rural town in the state of Minas Gerais, Brazil, following by first-degree and then increasingly more distant relatives. The first follow-up wave took place in 2010, and the second in 2016. At baseline, the study evaluated 1691 individuals across 95 families. Cross-sectional data have been collected for 2239 participants. Findings to date: Environmental and lifestyle factors and measures relevant to cardiovascular health have been reported. Having expanded beyond cardiovascular health outcomes, the phenotype datasets now include genetics, biochemistry, anthropometry, mental health, sleep and circadian rhythms. Many of these have yielded heritability estimates, and a shared genetic background of anxiety and depression has recently been published. In spite of universal access to electricity, the population has been found to be strongly shifted towards morningness compared with metropolitan areas. Future plans: A new follow-up, marking 10 years of the study, is ongoing in 2016, in which data are collected as in 2010 (with the exception of the neuropsychiatric protocol). In addition to this, a novel questionnaire package collecting information about intelligence, personality and spirituality is being planned. The data set on circadian rhythms and sleep will be amended through additional questionnaires, actimetry, home sleep EEG recording and dim light melatonin onset (DLMO) analysis. Finally, the anthropometric measures will be expanded by adding three-dimensional facial photography, voice recording and anatomical brain MRI.
- 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.
- Duffy blood group system: New genotyping method and distribution in a Brazilian extra-Amazonian population(2017) MARTINS, Marina Lobato; SILVA, Adao Rogerio da; SANTOS, Hadassa Campos; ALVES, Michelle Teodoro; SCHMIDT, Luciana Cayres; VERTCHENKO, Stela Brener; DUSSE, Luci Maria SantAna; MALTA, Maria Clara Fernandes da SilvaDuffy blood group system is of interest in several fields of science including transfusion medicine, immunology and malariology. Although some methods have been developed for Duffy polymorphism genotyping, not all of them have been sufficiently described and validated, and all present limitations. At the same time, the frequency of Duffy alleles and antigens in some densely populated regions of the world are still missing. In this study we present new tests for genotyping the major alleles of the Duffy blood system and describe Duffy alleles and antigens in blood donors and transfusion-dependent patients in Minas Gerais, Brazil. A simple and reproducible strategy was devised for Duffy genotyping based on real-time PCR that included SNPs rs12075 and rs2814778. No significant differences between the allele frequencies were observed comparing blood donors and patients. Among the blood donors, the phenotype Fy(a-b+) was the most common and the Fy(a-b-) phenotype, associated with populations of African descent, was remarkably less common among subjects who self-identified as black in comparison to other ethnoracial categories. However, the African ancestry estimated by molecular markers was significantly higher in individuals with the allele associated to the Duffy null phenotype. The genotyping method presented may be useful to study Duffy genotypes accurately in different contexts and populations. The results suggest a reduced risk of alloimmunization for Duffy antigens and increased susceptibility for malaria in Minas Gerais, considering the high frequency of Duffy-positive individuals.
conferenceObject Association between Amerindian (but not African or European) ancestry and diurnal preference (chronotype) within an admixed Brazilian population(2016) EGAN, K. J.; SANTOS, H. C.; DUARTE, N. E.; HORIMOTO, A. H. V. R.; KNUTSON, K. L.; PEREIRA, A. C.; SCHANTZ, M. von