Navegando por Palavras-chave "Genetics"

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    Adiponectin gene and cardiovascular risk in type 2 diabetic patients: a review of evidences
    (Sociedade Brasileira de Endocrinologia e Metabologia, 2007-03-01) Ferrarezi, Daniela Andraus de Figueiredo; Cheurfa, Nadir; Reis, André Fernandes [UNIFESP]; Fumeron, Frédéric; Velho, Gilberto [UNIFESP]; São Paulo University Laboratory of Cellular and Molecular Endocrinology; Universidade Federal de São Paulo (UNIFESP); Fleury Institute; INSERM; Université Paris 7
    Diabetic patients have a 3-fold higher risk of developing atherosclerosis and its clinical complications as compared to non-diabetic individuals. Part of the cardiovascular risk associated with diabetes is probably due to genetic determinants influencing both glucose homeostasis and the development of atherosclerosis. However, type 2 diabetes frequently coexists with other cardiovascular risk factors like arterial hypertension, central obesity and dyslipidemia. Genetic variability affecting many areas such as lipid and energy metabolisms, hypertension and haemodynamic mechanisms, blood clotting homeostasis, inflammation, and matrix turnover in the vascular wall will have an impact on the development of macrovascular complications in diabetic patients. Adiponectin is abundantly secreted by adipocytes. It plays important roles in lipid and glucose metabolisms and has direct anti-inflammatory and anti-atherogenic effects. In this review, we summarize recent data from the literature suggesting an implication of allelic variations of the adiponectin gene (ADIPOQ) in the genetic determinants of cardiovascular disease in diabetic subjects.
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    Alteração Da Expressão Gênica Relacionada A Sintomas Psicóticos E De Mania Em Pacientes Em Primeiro Episódio Psicótico Virgens De Tratamento
    (Universidade Federal de São Paulo (UNIFESP), 2017-05-31) Gouvea, Eduardo Sauerbronn [UNIFESP]; Belangero, Sintia Iole Nogueira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Psychoses are among serious mental disorders and affect approximately 3% of the general population. In the initial stages, the non-specific syndromic clinical aspects do not allow diagnostic clarity between the tables. The broad psychopathological nuance in the First Psychotic Episode (PEP) reinforces the need to investigate biomarkers that refine early diagnosis. We investigated the difference in gene expression among patients with schizophrenic symptoms (PEP-S, N = 53), with manifest symptoms (PEP-M, N = 16) and healthy controls (N = 76). We also analyzed the variation of gene expression with the severity of psychotic symptoms, manifested symptoms, depressive symptoms, and functional performance. All participants were treatment-naive with antipsychotics. After blood collection, 12 genes related to psychotic manifestations were evaluated by quantitative PCR. The expression levels of AKT1 and DICER1 were higher in patients with manifest symptoms (PEP-M) when compared to both patients with schizophrenic symptoms (PEP-S) and controls, suggesting that the expression of these genes is more specific to the occurrence of manifest symptoms . The expression of the MBP and NDEL1 genes was higher among the patients (both PEP-S and PEP-M) than in the healthy controls indicating a relationship with the psychotic manifestation itself independent of the diagnosis. We found no correlation between the levels of gene expression and the severity of symptoms or functional performance. Our findings suggest that the expression of genes related to neurodevelopment is altered in the psychoses, and can thus serve the differential diagnosis between schizophrenia and bipolar affective disorder and consequently to a better therapeutic definition.
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    Análise do polimorfismo de nucleotídeo único (SNP)RS2071307 selecionado no gene da elastina (ELN) em indivíduos do gênero masculino portadores de hérnia inguinal do tipo IIIa da Classificação de Nyhus
    (Universidade Federal de São Paulo (UNIFESP), 2020-11-26) Oliveira, Guilherme Blattner Torres De [UNIFESP]; Lopes Filho, Gaspar De Jesus [UNIFESP]; Universidade Federal de São Paulo
    Objectives: To evaluate the frequency of the single nucleotide polymorphism (SNP) rs2071307 in the ELN gene in male individuals with type IIIa inguinal hernia from the Nyhus classification, as well as to verify the association of this polymorphism with a positive family history in first-degree relatives degree for inguinal hernia. Methods: This is a case-control, multicenter and multidisciplinary study with 47 individuals submitted to inguinal herniorrhaphy and 50 individuals of the same age group, without a diagnosis of inguinal hernia. For this study, peripheral venous blood was collected from each individual, DNA extraction and genotyping by real-time PCR. Descriptive statistics included calculations of mean, median and standard deviation, as well as absolute and relative frequencies for categorical variables. Chi-square and Fisher's exact tests were used to assess the association between categorical variables. The Hardy-Weinberg balance was tested for the SNP in the case and control groups, as well as the chi-square test. To evaluate the association of the polymorphism and the occurrence of inguinal hernia, Odds ratios and the respective 95% confidence intervals were estimated. For all statistical tests, the results were considered statistically significant when p <0.05. All statistical analyzes were performed using the software Stata version 15.1. Results: The mean and median age of individuals with inguinal hernia were 48.3 and 40 years respectively (standard deviation: 14.1 years), whereas in controls, they were 40.4 and 50 years (standard deviation: 11, Four years). The genotypes of the groups were found in Hardy- Weinberg Equilibrium. The rs2071307 polymorphism and its respective GG, GA and AA genotypes showed a similar distribution between cases and controls (p = 0.499), with a predominance of the heterozygous GA genotype. The G allele was more frequent, being present in 86% of the sample between cases and controls. There was no statistical association between family history in first-degree relatives and inguinal hernia, both in cases with controls (p = 0.502 and p = 0.861, respectively). Conclusions: The rs2071307 polymorphism of the ELN gene, with its respective genotypes, was not associated with type IIIa inguinal hernia of the Nyhus classification, just as there was no association between this polymorphism and the presence of positive family history in first degree relatives for hernia. inguinal.
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    Análise dos polimorfismos ALA55VAL e inserção/deleção no exon 8 do gene da UCP-2 e suas relações com obesidade severa
    (Universidade Federal de São Paulo (UNIFESP), 2001) Vendramini, Marcio Faleiros [UNIFESP]; Moises, Regina Celia Mello Santiago [UNIFESP]
    As proteínas desacopladoras ("Uncoupling Proteins" - UCP) sao transportadores da membrana mitocondrial interna que dissipam o gradiente de prótons, liberando a energia estocada na forma de calor. Um dos subtipos desta proteína, a UCP-2, é largamente expressa no tecido adiposo branco em humanos, estando implicada no balanço energético em indivíduos adultos. Sendo a obesidade decorrente de um desbalanço entre o consumo calórico e o gasto energético, as UCPs tem sido investigadas como genes candidatos para a regulaçao do peso corporal. No presente estudo, investigamos associaçoes entre os polimorfismos Ala55Val no exon 4 e Inserçao / Deleçao de 45 pares de base no exon 8 do gene Ida UCP-2 com indicadores de obesidade e resistência à insulina. Foram selecionados 100 indivíduos portadores de obesidade severa (I.M.C. ? 40 kg/m2) e 70 indivíduos com I.M.C. entre 18 e 25 kg/m2, comparáveis em relaçao a idade e sexo Verificamos que a distribuiçao genotípica dos dois polimorfismos foi semelhante entre os indivíduos portadores de obesidade e os com peso adequado. Em relaçao ao polimorfismo Ala55Val no exon 4, os portadores de obesidade e carreadores do alelo Val apresentaram maiores níveis de pressao arterial sistólica (150 ñ 13,5 mmHg vs 140 ñ 19,3 mmHg; p= 0,024) quando comparados àqueles com genótipo Ala/Ala. Porém, em relaçao a outras variáveis antropométricas e metabólicas pesquisadas, nao encontramos associaçao com os polimorfismos. Em conclusao, na populaçao estudada, as variantes Ala55Val no exon 4 e Inserçao / Deleçao no exon 8 do gene da UCP-2 nao sao fatores contribuintes para a obesidade severa ou outras anormalidades metabólicas. Porém, é possível que a variante do exon 4 do gene da UCP-2 possa contribuir para a elevaçao de pressao arterial sistólica entre os portadores de obesidade.
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    Aspectos genéticos da escoliose idiopática do adolescente
    (Sociedade Brasileira de Coluna, 2012-09-01) Wajchenberg, Marcelo [UNIFESP]; Martins, Délio Eulálio; Puertas, Eduardo Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The adolescent idiopathic scoliosis is a common disease and its etiology remains unclear. Several hypotheses have been devised, including the possibility of genetic transmission. Studies in the literature have examined the prevalence of the disease in certain populations, the possible modes of transmission, the location of genes and variations of certain genes (polymorphisms) that may influence the development of the deformity. This article intends to review and update the concepts of genetic influence in the etiology of adolescent idiopathic scoliosis.
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    Aspectos genéticos do transtorno obsessivo-compulsivo
    (Associação Brasileira de Psiquiatria - ABP, 2001-10-01) Gonzalez, Christina H [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Since the first descriptions of obsessive-compulsive disorder (OCD), genetic factors have been implicated in the etiology of the illness. Twin studies show a high concordance rate for monozygotic twins. Family studies found a higher risk for OCD among relatives of OCD patients. Segregation analysis studies suggest the possible role of a major effect gene in the etiology of OCD. Association studies using molecular techniques have been conducted to try to find a specific gene or polymorphism involved in OCD. This review outlines the evidence gathered to date, including the recent findings in the molecular genetics analysis.
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    Associação de múltiplas variantes genéticas com a extensão e gravidade da doença coronária
    (Universidade Federal de São Paulo (UNIFESP), 2017-02-24) Fischer, Simone Cristina Pinto Matheus [UNIFESP]; Izar, Maria Cristina de Oliveira [UNIFESP]; http://lattes.cnpq.br/3734118596685936; http://lattes.cnpq.br/6991742643826788; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVES: Cardiovascular diseases, mainly ischemic heart disease and stroke, respond for the majority of deaths worldwide. Sedentary lifestyle and industrialized foods have determined na increase in metabolic diseases and cardiovascular risk. The concept of metabolic syndrome (MS) has emerged, and patients after an acute coronary syndrome (ACS) are associated with greater anatomic obstruction in the coronary tree. Despite the strong environmental influence, MS can be influenced in each componente by genetic variants. Polymorphisms related to lipid metabolism, lipid peroxidation, increase in blood pressure levels, and vascular reactivity can interact with environment to determine greater severity of coronary atherosclerosis in individuals with MS, acting sinergistically, even though the individual contribution of each genetic variant is small. Thus. The aim of this study was to examine the contribution of genetic polymorphisms on the extension and severity of coronary disease in subjects with MS and recente ACS. METHODS: One-hundred and sixteen patients of both genders, with three ormore criteria for MS (NCEP III) were prospectively evaluated, in the hospitalization period after na ACS. In this cross sectional study we performed clinical evaluation, laboratory parameters, assessment of inflammation and hemostasia markers, TBARS (thiobarbituric acid reactive substances), adiponectin, endotelial function (FMD). The extension and severity of coronary disease was assessed by measuring the Gensini score. Polymorphisms of the genes encoding paraoxonase-1 (PON-1), methylenotetrahydrofolato reductase (MTHFR), endothelial nitirc oxide sintase (ENOS), angiotensin-converting enzyme (ECA), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed using PCR-RFLP, with data presented according to genotype distribution. Statistical analyses used Chisquare, or Fisher’s exact test, for categorical variables and to test for deviation of the Hardy-Weinberg equilibrium. Numerical variables were compared by Student’s t testo r Mann-Whitney test, when appropriate. Pearson’s correlation test was also used. Significance was set at a P-value < 0.05. RESULTS: One-hundred and sixteen patients with MS in the hospital phase after na ACS, aging 56 + 9 years, 68% males, were evaluated. Polymorphisms of PON-1, MTHFR and ENOS were not in Hardy-Weinberg equilibrium. Many genotypes were associated with clinical variables, such as heart rate, diastolic blood pressure, or laboratory parameters like C-reactive protein, glycated hemoglobin, adiponectin, coagulation and fibrinolysis, in addition to associations with hormones or hepatic and muscle enzymes. Only the DD genotype of the D9N polymorphism of LPL was associated with greater severity and extension of coronary lesions. Genetic score was greater in patients with Gensini score < P50 (13.7 + 1.5 vs. 13.0 + 1.6, P=0.066). There was a weak inverse correlation between genetic score and Gensini score (R=-0.194, P=0.078). CONCLUSION: The polymorphisms studied had small contribution to the extension and severity of coronary disease. Only the D9N polymorphism of LPL has contributed to the severity of coronary disease in patients with MS after na ACS. Combined analyses of these polymorphismspresented weak association with severity of coronary disease, being the disease more severe with lower genetic score.
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    Associação entre fenótipo, desempenho com próteses auditivas e genótipo da deficiência auditiva infantil em crianças com e sem alteração genética
    (Sociedade Brasileira de Fonoaudiologia, 2012-01-01) Biaggio, Eliara Pinto Vieira; Azevedo, Marisa Frasson de [UNIFESP]; Iorio, Maria Cecilia Martinelli [UNIFESP]; Svidnicki, Maria Carolina Costa Melo; Satorato, Edi Lúcia; Universidade Federal de Santa Maria Departamento de Fonoaudiologia; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)
    PURPOSE: To establish the frequency of genetic mutations related to sensorineural hearing loss (SNHL); to verify if there is association between the degree of SNHL and the presence of genetic alteration; and to verify if the Minimal Response Levels (MRL) with hearing aids vary according to the genetic alteration. METHODS: Thirty hearing aids users with ages between 8 and 111 months were evaluated. The evaluation procedures used were: pure-tone audiometry; the auditory steady state response (ASSR) on sound field, with and without hearing aids; and genetic study of the hearing loss. RESULTS: Three genetic mutations were diagnosed: 35delG, A1555G and A827G, and the children with these mutations showed higher degree of SNHL. There was no difference between the genetic patterns regarding the degree of SNHL, except for patients with A827G mitochondrial mutation, because all subjects with this mutation had profound SNHL. The difference between the MRL obtained with and without amplification, considering the presence of mutation and the degree of SNHL, was higher in children with moderate SNHL without genetic alterations, both in behavioral and electrophysiological evaluations. CONCLUSION: Genetic mutations were found in 36.7% of the sample, justifying the importance of genetic tracking in the hearing habilitation process. Children with genetic mutations showed higher degrees of hearing loss. The different mutation patterns do not directly determine the degree of hearing loss. The best thresholds with amplification were found in children with moderate hearing loss without genetic alterations.
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    Associação entre perfil genético e posição de basquete em atletas da Liga Nacional Brasileira: um estudo transversal
    (Universidade Federal de São Paulo (UNIFESP), 2017-04-28) Lima, Giscard Humberto Oliveira [UNIFESP]; Pesquero, João Bosco [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction/Aim: In the last decades, advances in the studies of the genotypephenotype relationship have allowed the discovery of genetic biomarkers that are associated with phenotypes, such as sports performance in elite athletes of various modalities. Basketball is a sport that requires a complex combination of different characteristics and skills among players. Each player has a specific function inside the court and this function is directly related to her/his physical characteristics. The aim of the present study was to investigate whether there is an association between polymorphisms in genes related to performance (strength/power or endurance) and the player’s positions in basketball. Methodology: 154 athletes participated in the study; all of them competed in the National Basketball League 2012/2013. Polymorphisms in four genes related to sports performance were investigated. The polymorphisms in the angiotensin converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) genes were analyzed by standard PCR, and the polymorphisms in α-actinin 3 (ACTN3) and angiotensinogen (AGT) were analyzed by qPCR. In the statistical analysis SPSS software (version 21) was used. The GLM Univariate test was used In the analysis of height averages and the association between the genotypes and position were used the Multiple Logistic Regression and Multiple Correspondence Analysis tests. Results: The GLM test showed a significant effect of height on the positions. The Multiple Correspondence Analysis showed an association between the studied genotypes and the different positions in basketball. The Multiple Logistic Regression showed a higher prevalence of the different ACTN3 genotypes according to positions. We observed a positive association between the endurance genotypes with the point guard position, while the force/power related genotypes with the other positions, especially the power forward and center. Besides, more than half of the players with XX genotype of ACTN3 are point guards. Conclusion: The present study demonstrated that height is the main determinant of the position in the basketball, however this work also showed that there is an strong association between gene polymorphisms related to physical performance and player positions, mainly of the ACTN3. Therefore, we can conclude that the use of genetic information can help in understanding and enhancing the physical capacities of each player in this modality.
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    Avaliação do diagnóstico clínico e molecular de formas hereditárias de sensibilidade diminuída ao hormônio tireoidiano em um único centro terciário
    (Universidade Federal de São Paulo (UNIFESP), 2017) Ramos, Luciano Silva [UNIFESP]; Silva, Magnus Regios Dias da [UNIFESP]; Chiamolera, Maria Izabel [UNIFESP]; http://lattes.cnpq.br/1870589061538724; http://lattes.cnpq.br/2598816440086436; http://lattes.cnpq.br/7330510510151934; Universidade Federal de São Paulo (UNIFESP)
    Conclusões " A maioria dos casos desta série apresenta RTH com mutação no THR", similar ao encontrado na literatura, porém em menor percentagem (74% v.s. 85%); " a alteração molecular mais comum foi no códon 453 do THR", o mesmo encontrado na literatura; " três novas mutações no THR" foram encontradas neste estudo: P.M131v, P.R320g E P.R438p; " deve-se suspeitar de RHT, TSH-OMA e HDF em todo paciente com TSH não suprimido associado ao T4l elevado; " pacientes com RHT podem apresentar taquicardia e bócio, enquanto pacientes com TSH-OMA apresentam mais frequentemente características clínicas de tirotoxicose e pacientes com HDF são frequentemente assintomáticos; " devido à falta de características bioquímicas específicas entre RHT, TSH-OMA e HDF, o teste molecular é de suma importância para evitar diagnóstico errôneo e, consequentemente, tratamento desnecessário; " os principais diagnósticos diferenciais foram de TSH-OMA e HDF, embora este último não seja considerado uma causa importante de TSH inapropriadamente.
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    Bases Genéticas do Diabetes Mellitus Tipo 2
    (Sociedade Brasileira de Endocrinologia e Metabologia, 2002-08-01) Reis, André Fernandes [UNIFESP]; Velho, Gilberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The pathogenesis of type 2 diabetes mellitus (T2DM) is complex, but it is secondary to a combination of insulin resistance and pancreatic beta-cell dysfunction that manifests itself as inadequate insulin secretion in the face of hyperglycemia. Several studies have established a clear genetic predisposition for T2DM. Some genes for monogenic forms of diabetes have been identified (MODY, mitochondrial diabetes). However, few genes were found to be associated with diabetes in the more common forms of T2DM. In these T2DM forms, a variety of environmental factors play a major role in the clinical expression of disease. This article addresses the clinical and genetic advances in the genetic bases of T2DM.
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    Clinical presentation and genetic paradigm of diffuse infiltrating retinoblastoma: a review
    (Acta Cirurgica Brasileira, 2016) Traine, Peter G.; Schedler, Katharina J.; Rodrigues, Eduardo B. [UNIFESP]
    Retinoblastoma is the most common childhood cancer. Thanks to modern technology and good medical access, mortality in Europe has decreased to about 5%. Diffuse infiltrating retinoblastoma is a very rare subtype of this neoplasm and is characterized by its atypical growth pattern. Diffuse infiltrating retinoblastoma may mimic other more innocuous diseases and may therefore be misdiagnosed. The purpose of this paper was to provide a short review of the main symptoms of diffuse infiltrating retinoblastoma presenting to the ophthalmologist and give a comparison to typical retinoblastoma. The second purpose was to set up a discussion of the genetic paradigm of diffuse infiltrating retinoblastoma. It has often been described to occur sporadically
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    Diabetes Mellitus do Tipo MODY
    (Sociedade Brasileira de Endocrinologia e Metabologia, 2002-04-01) Oliveira, Carolina Soares Viana de [UNIFESP]; Furuzawa, Gilberto K. [UNIFESP]; Reis, André Fernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    It is estimated that close to 5% of the individuals classified as having type 2 diabetes mellitus (DM) and about 10% of those considered type 1 DM (previously categorized as juvenile type) are actual carriers of a MODY mutation. In this form of DM, there is evident co-segregation of some mutations and the advent of hyperglycemia, this fact having been reproduced by the study of several families of different populations. Its main characteristic is being one of the few causes of DM in which the transmission of the genetic susceptibility is due to an autossomical dominant inheritance, making part of the group classified as monogenic DM, where the other members are very rare. Mutations occurring in MODY genes, even in the heterozygous form, lead to a profound phenotypic impact (high penetrance), in that 95% of the individual carriers of a MODY mutation will be diabetic or will have altered glicemic metabolism before the age of 55 years. In this paper we approach this form of DM, emphasizing its most relevant clinical and genetic characteristics. The systematic search for MODY mutations is beginning to take place regularly in many countries, and there is a tendency to add this diagnostic tool to the routine exams in the practice of diabetology.
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    The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description
    (Associação Brasileira de Psiquiatria - ABP, 2009-12-01) Hoexter, Marcelo Queiroz [UNIFESP]; Shavitt, Roseli Gedanke; D'Alcante, Carina Chaubet; Cecconi, Janaina Philippi; Diniz, Juliana Belo; Belotto-Silva, Cristina; Hounie, Ana Gabriela; Borcato, Sonia; Moraes, Ivanil; Joaquim, Marines Alves; Cappi, Carolina; Sampaio, Aline Santos; Mathis, Maria Alice de; Batistuzzo, Marcelo Camargo; Lopes, Antonio Carlos [UNIFESP]; Rosa, Ana Carolina Ferreira; Muniz, Renan Kawano; Marques, Andrea Horvath; Santos, Luciana Cristina; Taub, Anita; Duran, Fábio Luís de Souza; Dougherty, Darin Dean; Busatto Filho, Geraldo [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Miguel, Euripedes Constantino; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Harvard Medical School Massachusetts General Hospital Department of Psychiatry; Hospital Israelita Albert Einstein Instituto Israelita de Ensino e Pesquisa
    OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.
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    Escoliose idiopática do adolescente: estudo familiar para identificação de regiões cromossômicas ligadas à sua etiologia
    (Universidade Federal de São Paulo (UNIFESP), 2010-05-26) Wajchenberg, Marcelo [UNIFESP]; Ishida, Akira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: The etiology of idiopathic scoliosis remains unknown and different factors have been suggested as causal. Hereditary factors can also determine the etiology of the disease; however, the pattern of inheritance remains unknown. Other studies have suggested possible chromosome regions related to the etiology of idiopathic scoliosis. Objetive: To study the genetic aspects and investigate chromosome regions for adolescent idiopathic scoliosis in a Brazilian family. Methods: Evaluation of 56 family members, distributed over 4 generations of a Brazilian family, with 9 carriers of adolescent idiopathic scoliosis. The proband presented a scoliotic curve of 75 degrees, as determined by the Cobb method. Genomic DNA from family members was genotyped. Results: Locating a chromosome region linked to adolescent idiopathic scoliosis was not possible in the family studied. Conclusion: While it was not possible to determine a chromosome region responsible for adolescent idiopathic scoliosis by investigation of genetic linkage using microsatellites markers during analysis of four generations of a Brazilian family with multiple affected members.
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    Estudo clínico e molecular em pacientes com artrogripose distal
    (Universidade Federal de São Paulo (UNIFESP), 2017-02-22) Nicola, Pablo Domingos Rodrigues De [UNIFESP]; Perez, Ana Beatriz Alvarez [UNIFESP]; Abath Neto, Osório Lopes; http://lattes.cnpq.br/4784102068388854; http://lattes.cnpq.br/8077340861513133; Universidade Federal de São Paulo (UNIFESP)
    Distal Arthrogryposis (DA) is a group of monogenic diseases of autosomal dominant inheritance, with incomplete penetrance, variable expressivity, characterized by congenital contractions of the distal joints of the limbs, not being caused by defects of the central and peripheral nervous system, by myopathies or by metabolic diseases. Ten different syndromes make up this group, the most common being DA1, DA2A and DA2B. Mutations in genes encoding skeletal muscle proteins (ECEL1, FBN2, MYBPC1, MYH3, MYH8, TNNI2, TNNT3, TPM2 and PIEZO2) are responsible for the etiology of AD. Objective: To describe clinical and molecular findings in patients with AD. To study the genes ACTA1, MYBPC1, MYH3, MYH8, TNNI2, TNNT1, TNNT3 and TPM2, in patients with AD and in their respective parents. To classify patients into syndromic groups and into molecular groups. Method: Evaluation of patients with congenital multiple arthrogryposis according to the clinical protocol. Extraction of genomic DNA from peripheral blood. State-of-the-art sequencing (NGS) using a panel of 8 genes (ACTA1, MYBPC1, MYH3, MYH8, TNNI2, TNNT1, TNNT3, TPM2). Validation of variants found in NGS by performing Sanger sequencing. Results: Among 106 patients with congenital multiple arthrogryposis, 19 subjects fulfilled the inclusion criteria for AD, 14 sporadic cases and 5 familial cases. Among the 19 individuals with AD, 7 individuals presented variants considered pathogenic, being 4 sporadic cases and 3 cases in the same family. Conclusions: Three variants of the MYH3 gene (c.1402T> C, c.2015G> A and c.5254G> T) were reported in individuals with DA1, DA2A and DA2B, two variants never described in the literature; one in the MYH8 gene (c.3349 + 1G> T) in an individual with DA7, not reported in the literature; and one in the TNNT3 gene (c.187C> T) in a sporadic case of DA2B and in 3 familial cases with DA2B that present phenotypic variability.
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    Estudo de associação genética em larga escala identifica potenciais regiões candidatas para o bruxismo do sono
    (Universidade Federal de São Paulo (UNIFESP), 2017-01-31) Amaral Junior, Rosalvo [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Hirotsu, Camila; http://lattes.cnpq.br/0254842686561012; http://lattes.cnpq.br/4951931552005515; http://lattes.cnpq.br/8801997569397443; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Sleep bruxism is usually associated with excessive dental attrition and fractures or other health problems, such as morning headaches, muscle pain and increased risk of some temporomandibular disorders. Some evidence suggests that its pathophysiology may be influenced by genetic factors. Objectives: The present study aimed to evaluate potential polymorphisms, genes and biological pathways associated with sleep bruxism. Methods: It was performed a cross-sectional genome-wide association study with 75 sleep bruxism cases and 568 controls, all of them extracted from EPISONO cohort. Sleep bruxism was diagnosed by polysomnography and questionnaires. The DNA of all individuals was extracted from peripheral blood and 730,025 single nucleotide polymorphisms (SNPs) were genotyped through microarrays. Results: The results showed 2 SNPs associated with sleep bruxism with significance level <10-5: rs741448 located in 19q12 (p=5.12 x10-6); rs1721781 located in 2p22.3 (p=7.18 x10-6) and 38 SNPs with significance <10-4. In addition, through gene pathway and biological pathway analysis, associations with genes such as EPN3 (Epsin 3) with significance level <10-4 and biological pathways such as Melanin biosynthesis with significance level 10-3 were found between others not yet explored by pathophysiological hypothesis of sleep bruxism. Conclusions: This is the first study that identified genetic association with sleep bruxism. When replicated, it may point to new hypotheses in the pathophysiology of sleep bruxism.
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    Estudo de associação genética no angioedema induzido por anti-inflamatórios não-esteroidais
    (Universidade Federal de São Paulo (UNIFESP), 2017-12-15) Ensina, Luis Felipe Chiaverini [UNIFESP]; Solé, Dirceu [UNIFESP]; Pesquero, João Bosco [UNIFESP]; http://lattes.cnpq.br/0856630824759511; http://lattes.cnpq.br/8188258243306974; http://lattes.cnpq.br/1710760985911599; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Non-steroidal anti-inflammatory drugs (NSAID) are the main cause of drugs hypersensitivity reactions in our circle. Non-selective hypersensitive is the most common type, occurring with any NSAID, independently of its chemical structure, and presenting with anaphylaxis, urticaria or angioedema. The mechanism involved is supposedly related to the cyclooxygenase inhibition, and genetic polymorphisms that regulate or increase the expression of leukotrienes related genes could be risk factors for NSAID hypersensitivity. Objectives: To detect possible genetic markers by exome sequencing, that determine a hypersensitivity response in patients with NSAID induced isolated angioedema. Methods: We selected four trios (patients with an isolated angioedema induced by multiple NSAID and its respective parents) for exome sequencing, a technic that allows checking the biologic active part of the genome (exons). Results: It was not possible to determine any significant biological variable in the genes related to arachidonic acid metabolism, or in any of the other genes previously related to NSAID hypersensitivity. We observed a polymorphism in gene MUC5B in three of the four families, possibly indicating the existence of other mechanisms related to the reaction. Conclusions: We did not find any mutation directly related to NSAID induced angioedema in the studied group. A validation and deeply study of the biological effects of the MUC5B variable in the families studies should be performed.
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    Acesso aberto (Open Access)
    Estudo do perfil genético e molecular do sistema calicreína-cininas em pacientes portadores de hipercolesterolemia familiar
    (Universidade Federal de São Paulo (UNIFESP), 2019-03-28) Bittencourt, Clarissa Azevedo [UNIFESP]; Pesquero, Joao Bosco [UNIFESP]; http://lattes.cnpq.br/0856630824759511; http://lattes.cnpq.br/6475256598464720; Universidade Federal de São Paulo (UNIFESP)
    Familial hypercholesterolemia is an autosomal dominant genetic disorder characterized by increased serum levels of total cholesterol and low-density lipoprotein cholesterol. Familial hypercholesterolemia is directly related to the development of cardiovascular diseases, such as hypertension, atherosclerosis, myocardial infarction and coronary disease. In this context, the kallikrein-kinin system actively participates in the regulation of cardiovascular system functions, as demonstrated in studies with angiotensin-converting enzyme inhibitors and has cardioprotective effects mediated by the direct release of nitric oxide by endothelium or stimulated by prostaglandins. No study has so far associated the contribution of the kallikrein-kinin system in the modulation of symptoms or in the pathogenesis of familial hypercholesterolemia. Thus, in this work we investigated the genetic profile of the kallikrein-kinin system in patients with familial hypercholesterolemia. The new generation sequencing of eleven genes related to the kallikrein-kinin system were carried out in 102 patients with familial hypercholesterolemia. 22 rare variants were identified, with nine variants classified as pathogenic by in silico predictors; and 14 polymorphisms. Eight of these variants, present in the ACE, KLK1 and KNG1 genes may be candidate variants to be related to systemic arterial hypertension. Despite the limitations of the association between genotype and phenotype, the results obtained in this work open the opportunity to expand knowledge about the possible modulation of the kallikrein-kinin system in the development of cardiovascular diseases, particularly hypertension, in the context of familial hypercholesterolemia.
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    Somente Metadadados
    Estudo genealógico de 100 pacientes brasileiros com escoliose idiopática do adolescente
    (Universidade Federal de São Paulo (UNIFESP), 2004) Wajchenberg, Marcelo [UNIFESP]; Puertas, Eduardo Barros [UNIFESP]
    Objetivo: Avaliar a prevalência da escoliose idiopática do adolescente uma população brasileira e estudar os heredogramas desta popular Métodos: Foram examinados e acompanhados em ambulatório, pacientes brasileiros com escoliose idiopática do adolescente no período entre 1998 a 2003, realizando seus heredogramas por meio de entrevi para estudo da prevalência familiar e análise das possíveis formas transmissão genética. Resultados: A prevalência encontrada foi de 5,2 entre parentes de primeiro grau e de 4,54 por cento entre parentes de segundo gr com taxa de consangüinidade de 3 por cento entre a população estudada. A avalia dos heredogramas demonstra situações que sugerem tanto a um padrão herança autossômica recessiva como uma herança multifatorial. Conclusão A escoliose idiopática do adolescente é uma doença que apresenta heterogeneidade genética com vários genes envolvidos, alguns com herança Mendeliana e outros obedecendo a uma herança multifatorial. Estes são primeiros dados referentes à escoliose idiopática do adolescente em nosso meio, sendo necessário estudos mais detalhados para analisar os possíveis mecanismos de transmissão desta doença.