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Association between polymorphisms in modifier genes in children and adolescent with allergic and non-allergic: mild, moderate and severe asthma

Grant number: 11/12939-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2012
Effective date (End): July 31, 2015
Field of knowledge:Health Sciences - Medicine
Principal researcher:Jose Dirceu Ribeiro
Grantee:Fernando Augusto de Lima Marson
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Introduction: Asthma is a chronic inflammatory disease that has a high prevalence of different degrees of severity. Although many current studies, is not known completely, the genetic environmental interactions in this disease, but it is known that several genes and environmental factors act on the severity and etiology of asthma. In our study, we selected polymorphisms in genes modulators, previously reported as possible active in metabolic pathways that influence asthma: ACE and CD14 (pro-inflammatory properties), ALOX5AP and LTA4H (active in the biological cycle that leads to the production of LTB4), GCLC and GST [M1, P1 and T1] (active cycle of glutathione and oxidative stress-related), IL4 [cytokine that induces differentiation of undifferentiated Th cells (Th0) to Th2 cells], IL4R (receptor that binds IL-4 and IL-13 to regulate the production of IgE antibodies), IL13 (acting in allergic inflammation), IL1R1 (expression by pro-inflammatory stimuli and involved in the function of Th cells), NOS-1 (associated with eosinophilic inflammation), STAT6 (activator transcription and serves on the biological response mediated by IL-4), TGFB1 (limited inflammatory reactions and acts in tissue repair and remodeling), TLR2 and TLR4 (recognize foreign substances and transmit signals to the activation of the immune system). Objective: To characterize patients with atopic asthma and nonatopic of the Pediatric Clinic of HC/UNICAMP second questionnaire of clinical severity, determine the frequency of different polymorphisms and associate both with the aim of understanding the presentation of the disease. Method: Cross-sectional study, prospective. Will be carried out DNA extraction kit for DNA extraction Flexigene Quiagen Kit ®, analysis of polymorphisms in the ACE gene, GSTM1 and T1 by conventional PCR, genotyping for the NOS-1 gene, and analysis of polymorphisms of SNPs for type technique Open Array [OpenArray ® TaqMan ® Genotyping (Applied Biosystems by Life Technologies ®)] of 500 patients with asthma and 500 controls. The classification of severity and classification for control of the same will be held on the basis DBMA (2006) for all patients. Testing will be performed logistic and linear regression for each polymorphism in relation to data obtained from patients. The analysis will be performed by the software "Statistical Package for the Social Sciences" (SPSS) v.17.0, with adjustments for multiple tests by Bonferroni test.

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Scientific publications (36)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PEIXOTO, ANDRESSA O.; AL MARSON, FERNANDO; DERTKIGIL, SERGIO SJ; DERTKIGIL, RAQUEL P.; SOUZA, TIAGO H.; FRAGA, ANDREA; RIBEIRO, ANTONIO F.; TORO, ADYLEIA ADC; RIBEIRO, JOSE D.. The Use of Ultrasound as a Tool to Evaluate Pulmonary Disease in Cystic Fibrosis. Respiratory Care, v. 65, n. 3, p. 293-303, . (11/12939-4, 15/12183-8, 11/18845-1, 15/12858-5)
LIMA MARSON, FERNANDO AUGUSTO; BERTUZZO, CARMEN SILVIA; DE ARAUJO, TANIA KAWASAKI; RUSSO HORTENCIO, TAIS DAIENE; RIBEIRO, ANTONIO FERNANDO; RIBEIRO, JOSE DIRCEU. Pancreatic Insufficiency in Cystic Fibrosis: Influence of Inflammatory Response Genes. PANCREAS, v. 47, n. 1, p. 99-109, . (11/18845-1, 15/12858-5, 11/12939-4, 15/12183-8)
CAMARGO BARROS ROCHA, D. A.; MARSON, F. A. L.; ALMEIDA, C. C. B.; ALMEIDA JUNIOR, A. A.; RIBEIRO, J. D.. Association between oxygenation and ventilation indices with the time on invasive mechanical ventilation in infants. PULMONOLOGY, v. 24, n. 4, p. 241-249, . (11/12939-4, 15/12183-8, 11/18845-1, 15/12858-5)
SOUZA GOMEZ, CARLA CRISTINA; FRANCISCO PARAZZI, PALOMA LOPES; CLINCKSPOOR, KARL JAN; MAUCH, RENAN MARRICHI; TEIXEIRA PESSINE, FRANCISCO BENEDITO; LEVY, CARLOS EMILIO; PEIXOTO, ANDRESSA OLIVEIRA; GONCALVES OLIVEIRA RIBEIRO, MARIA ANGELA; RIBEIRO, ANTONIO FERNANDO; CONRAD, DOUGLAS; et al. Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis. CLINICAL DRUG INVESTIGATION, . (11/12939-4, 15/12858-5, 15/12183-8, 11/18845-1)
PALOMA L.F. PARAZZI; FERNANDO A.L. MARSON; MARIA A.G.O. RIBEIRO; CAMILA I.S. SCHIVINSKI; JOSÉ D. RIBEIRO. Avaliação da dinâmica respiratória por capnografia volumétrica durante o protocolo de exercício submáximo por seis minutos em esteira em pacientes com fibrose cística. Jornal de Pediatria, v. 95, n. 1, p. 76-86, . (15/12183-8, 11/18845-1, 15/12858-5, 11/12939-4)
COUTINHO, C. A. A. C.; MARSON, F. A. L.; RIBEIRO, J. D.; BERTUZZO, C. S.. A negative screening of rare genetic variants in the ADIPOQ and STATH genes in cystic fibrosis. PULMONOLOGY, v. 26, n. 3, p. 138-144, . (11/12939-4, 15/12183-8, 11/18845-1, 15/12858-5)
PARAZZI, PALOMA L. F.; MARSON, FERNANDO A. L.; RIBEIRO, MARIA A. G. O.; SCHIVINSKI, CAMILA I. S.; RIBEIRO, JOSE D.. Evaluation of respiratory dynamics by volumetric capnography during submaximal exercise protocol o six minutes on treadmill in cystic fibrosis patients. Jornal de Pediatria, v. 95, n. 1, p. 76-86, . (11/12939-4, 15/12858-5, 15/12183-8, 11/18845-1)
FARIA, ALETHEA GUIMARAES; LIMA MARSON, FERNANDO AUGUSTO; SOUZA GOMEZ, CARLA CRISTINA; SERVIDONI, MARIA DE FATIMA; RIBEIRO, ANTONIO FERNANDO; RIBEIRO, JOSE DIRCEU. Thirty Years of Sweat Chloride Testing at One Referral Center. FRONTIERS IN PEDIATRICS, v. 5, . (11/18845-1, 15/12858-5, 11/12939-4, 15/12183-8)
FURGERI, DANIELA TENORIO; LIMA MARSON, FERNANDO AUGUSTO; ARAUJO CORREIA, CYNTIA ARIVABENI; RIBEIRO, JOSE DIRCEU; BERTUZZO, CARMEN SILVIA. Cystic fibrosis transmembrane regulator haplotypes in households of patients with cystic fibrosis. Gene, v. 641, p. 137-143, . (11/12939-4, 15/12858-5, 15/12183-8, 11/18845-1)
FURLAN, LARISSA LAZZARINI; RIBEIRO, JOSE DIRCEU; BERTUZZO, CARMEN SILVIA; SALOMAO JUNIOR, JOAO BATISTA; SILVA SOUZA, DOROTEIA ROSSI; LIMA MARSON, FERNANDO AUGUSTO. Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis. Jornal de Pediatria, v. 93, n. 6, p. 639-648, . (11/18845-1, 15/12183-8, 11/12939-4, 13/19052-0, 15/12858-5)
MARSON, FERNANDO A. L.; BERTUZZO, CARMEN S.; RIBEIRO, JOSE D.. Personalized or Precision Medicine? The Example of Cystic Fibrosis. FRONTIERS IN PHARMACOLOGY, v. 8, . (11/18845-1, 15/12858-5, 11/12939-4, 15/12183-8)
PEREIRA, STEPHANIE VILLA-NOVA; RIBEIRO, JOSE DIRCEU; BERTUZZO, CARMEN SILVIA; LIMA MARSON, FERNANDO AUGUSTO. Association of clinical severity of cystic fibrosis with variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3). Gene, v. 629, p. 117-126, . (11/18845-1, 15/12858-5, 11/12939-4, 15/12183-8)
SOUZA GOMEZ, CARLA CRISTINA; LIMA MARSON, FERNANDO AUGUSTO; SERVIDONI, MARIA FATIMA; RIBEIRO, ANTONIO FERNANDO; GONCALVES OLIVEIRA RIBEIRO, MARIA ANGELA; LOPES GAMA, VERUSKA ACIOLI; COSTA, EDUARDO TAVARES; RIBEIRO, JOSE DIRCEU; VIEIRA JUNIOR, FRANCISCO UBALDO. Evaluation of continuous constant current and continuous pulsed current in sweat induction for cystic fibrosis diagnosis. BMC PULMONARY MEDICINE, v. 18, . (11/12939-4, 15/12858-5, 15/12183-8, 11/18845-1)
MARIANA S. FERREIRA; ROBERTO T. MENDES; FERNANDO A.L. MARSON; MARIANA P. ZAMBON; MARIA A.R.G.M. ANTONIO; ILMA A. PASCHOAL; ADYLÉIA A.D.C. TORO; SILVANA D. SEVERINO; MARIA A.G.O. RIBEIRO; JOSÉ D. RIBEIRO. Espirometria e capnografia volumétrica na avaliação da função pulmonar de indivíduos obesos e eutróficos sem asma. Jornal de Pediatria, v. 93, n. 4, p. 398-405, . (15/12183-8, 11/18845-1, 15/12858-5, 11/12939-4)
SOUZA GOMEZ, CARLA CRISTINA; SERVIDONI, MARIA DE FATIMA; DE LIMA MARSON, FERNANDO AUGUSTO; COELHO CANAVEZI, PAULO JOSE; VINAGRE, ADRIANA MENDES; COSTA, EDUARDO TAVARES; RIBEIRO, ANTONIO FERNANDO; GONCALVES DE OLIVEIRA RIBEIRO, MARIA ANGELA; DALBO CONTRERA TORO, ADYLEIA APARECIDA; PAVAN, CELIA REGINA; et al. Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test. BMC PULMONARY MEDICINE, v. 14, . (11/12939-4)
MARIA FÁTIMA SERVIDONI; CARLA CRISTINA SOUZA GOMEZ; FERNANDO AUGUSTO LIMA MARSON; ADYLÉIA APARECIDA DALBO CONTRERA TORO; MARIA ÂNGELA GONÇALVES DE OLIVEIRA RIBEIRO; JOSÉ DIRCEU RIBEIRO; ANTÔNIO FERNANDO RIBEIRO. Teste do suor e fibrose cística: panorama da realização do teste em centros públicos e privados do estado de São Paulo. Jornal Brasileiro de Pneumologia, v. 43, n. 2, p. 121-128, . (15/12858-5, 11/12939-4)
PARAZZI, P. L. F.; MARSON, F. A. L.; RIBEIRO, M. A. G. O.; SCHIVINSKI, C. I. S.; RIBEIRO, J. D.. Correlation between parameters of volumetric capnography and spirometry during a submaximal exercise protocol on a treadmill in patients with cystic fibrosis and healthy controls. PULMONOLOGY, v. 25, n. 1, p. 21-31, . (11/12939-4, 15/12183-8, 11/18845-1, 15/12858-5)
MARSON, FERNANDO A. L.. Disease-modifying genetic factors in cystic fibrosis. CURRENT OPINION IN PULMONARY MEDICINE, v. 24, n. 3, p. 296-308, . (11/12939-4, 15/12858-5)
DENTINI, PRISCILA; LIMA MARSON, FERNANDO AUGUSTO; BONADIA, LUCIANA CARDOSO; BERTUZZO, CARMEN SILVIA; RIBEIRO, ANTONIO FERNANDO; LEVY, CARLOS EMILIO; RIBEIRO, JOSE DIRCEU. Burkholderia cepacia complex in cystic fibrosis in a Brazilian reference center. MEDICAL MICROBIOLOGY AND IMMUNOLOGY, v. 206, n. 6, p. 447-461, . (11/12939-4, 15/12858-5, 15/12183-8, 11/18845-1)
WOLLMEISTER, ELINARA; ALVAREZ, ALFONSO EDUARDO; SANTIAGO BASTOS, JULIANA CRISTINA; LIMA MARSON, FERNANDO AUGUSTO; RIBEIRO, JOSE DIRCEU; ELIAS BARACAT, EMILIO CARLOS; ARNS, CLARICE WEIS; LOPES RICCETTO, ADRIANA GUT. Respiratory syncytial virus in Brazilian infants - Ten years, two cohorts. Journal of Clinical Virology, v. 98, p. 33-36, . (11/12939-4, 15/12183-8, 11/18845-1, 15/12858-5)
LARISSA LAZZARINI FURLAN; JOSÉ DIRCEU RIBEIRO; CARMEN SÍLVIA BERTUZZO; JOÃO BATISTA SALOMÃO JUNIOR; DOROTÉIA ROSSI SILVA SOUZA; FERNANDO AUGUSTO LIMA MARSON. Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalatórios na fibrose cística,. Jornal de Pediatria, v. 93, n. 6, p. 639-648, . (15/12858-5, 15/12183-8, 11/18845-1, 11/12939-4, 13/19052-0)
GONCALVES BONALDO, TAISA CRESPI; SOUZA GOMEZ, CARLA CRISTINA; FRANCISCO PARAZZI, PALOMA LOPES; BRESCIANI ALMEIDA, CELIZE CRUZ; LIMA MARSON, FERNANDO AUGUSTO; DE OLIVEIRA, THEREZINHA; ALVES GRANDE, ROSANGELA APARECIDA; COHEN, MILENA ANTONELLI. Use of Non-Invasive Ventilation in Children and Adolescents: Scientific Evidence. CURRENT RESPIRATORY MEDICINE REVIEWS, v. 13, n. 2, p. 82-92, . (11/12939-4, 15/12183-8, 11/18845-1, 15/12858-5)
FURLAN, LARISSA LAZZARINI; LIMA MARSON, FERNANDO AUGUSTO; RIBEIRO, JOSE DIRCEU; BERTUZZO, CARMEN SILVIA; SALOMAO JUNIOR, JOAO BATISTA; SILVA SOUZA, DOROTEIA ROSSI. IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability. Human Genetics, v. 135, n. 8, p. 881-894, . (11/18845-1, 11/12939-4, 15/12858-5, 13/19052-0)
REZENDE, LUCIANA MONTES; LIMA MARSON, FERNANDO AUGUSTO; PASSOS LIMA, CARMEN SILVIA; BERTUZZO, CARMEN SILVIA. Variants of estrogen receptor alpha and beta genes modify the severity of sporadic breast cancer. Gene, v. 608, p. 73-78, . (11/12939-4, 15/12858-5)
FRANCISCO PARAZZI, PALOMA LOPES; DE LIMA MARSON, FERNANDO AUGUSTO; GONCALVES DE OLIVEIRA RIBEIRO, MARIA ANGELA; BRESCIANI DE ALMEIDA, CELIZE CRUZ; MARTINS, LUIZ CLAUDIO; PASCHOAL, ILMA APARECIDA; DALBO CONTRERA TORO, ADYLEIA APARECIDA; SANTOS SCHIVINSKI, CAMILA ISABEL; RIBEIRO, JOSE DIRCEU. Ventilatory abnormalities in patients with cystic fibrosis undergoing the submaximal treadmill exercise test. BMC PULMONARY MEDICINE, v. 15, . (11/12939-4)
FRANCISCO PARAZZI, PALOMA LOPES; DE LIMA MARSON, FERNANDO AUGUSTO; GONCALVES DE OLIVEIRA RIBEIRO, MARIA ANGELA; SANTOS SCHIVINSKI, CAMILA ISABEL; RIBEIRO, JOSE DIRCEU. Ventilatory Efficiency in Children and Adolescents: A Systematic Review. DISEASE MARKERS, . (11/12939-4)
FARIA, ALETHEA GUIMARAES; LIMA MARSON, FERNANDO AUGUSTO; DE SOUZA GOMEZ, CARLA CRISTINA; GONCALVES DE OLIVEIRA RIBEIRO, MARIA ANGELA; MORAIS, LUCAS BRIOSCHI; SERVIDONI, MARIA DE FATIMA; BERTUZZO, CARMEN SILVIA; SAKANO, EULALIA; GOTO, MAURA; PASCHOAL, ILMA APARECIDA; et al. Quality of sweat test (ST) based on the proportion of sweat sodium (Na) and sweat chloride (Cl) as diagnostic parameter of cystic fibrosis: are we on the right way?. DIAGNOSTIC PATHOLOGY, v. 11, . (11/12939-4, 11/18845-1, 15/12858-5)
DE LIMA MARSON, FERNANDO AUGUSTO; RUSSO HORTENCIO, TAIS DAIENE; ALBERTO AGUIAR, KATIA CRISTINA; RIBEIRO, JOSE DIRCEU; GRP, CYFIUC. Demographic, clinical, and laboratory parameters of cystic fibrosis during the last two decades: a comparative analysis. BMC PULMONARY MEDICINE, v. 15, . (11/12939-4)
DE LIMA MARSON, FERNANDO AUGUSTO; BERTUZZO, CARMEN SILVIA; RIBEIRO, JOSE DIRCEU. Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality. CURRENT DRUG TARGETS, v. 16, n. 9, p. 1007-1017, . (11/12939-4)
ARMANDO ALMEIDA-JUNIOR; FERNANDO AUGUSTO LIMA MARSON; CELIZE CRUZ BRESCIANI ALMEIDA; MARIA ÂNGELA GONÇALVES OLIVEIRA RIBEIRO; ILMA APARECIDA PASCHOAL; MARCOS MELLO MOREIRA; JOSÉ DIRCEU RIBEIRO. Capnografia volumétrica versus espirometria para avaliação da função pulmonar na fibrose cística e na asma alérgica,. Jornal de Pediatria, v. 96, n. 2, p. 255-264, . (15/12183-8, 11/18845-1, 15/12858-5, 11/12939-4)
PEREIRA, STEPHANIE V. N.; RIBEIRO, JOSE D.; BERTUZZO, CARMEN S.; MARSON, FERNANDO A. L.. Interaction among variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1, and SLC9A3) and CFTR mutations with clinical markers of cystic fibrosis. PEDIATRIC PULMONOLOGY, v. 53, n. 7, p. 888-900, . (11/12939-4, 11/18845-1, 15/12858-5, 15/12183-8)
AGUIAR, K. C. A.; MARSON, F. A. L.; GOMEZ, C. C. S.; PEREIRA, M. C.; PASCHOAL, I. A.; RIBEIRO, A. F.; RIBEIRO, J. D.. Physical performance, quality of life and sexual satisfaction evaluation in adults with cystic fibrosis: An: unexplored correlation. Revista Portuguesa de Pneumologia, v. 23, n. 4, p. 179-192, . (11/18845-1, 11/12939-4, 15/12858-5, 15/12183-8, 12/05458-2)
FARIA, A. G.; MARSON, F. A. L.; RIBEIRO, A. F.; RIBEIRO, J. D.. The correlation between age and sweat chloride levels in sweat tests. Revista Portuguesa de Pneumologia, v. 23, n. 4, p. 227-230, . (11/18845-1, 15/12858-5, 11/12939-4, 15/12183-8)
MARQUES FERREIRA, ADRIANA CAROLINA; LIMA MARSON, FERNANDO AUGUSTO; COHEN, MILENA ANTONELLI; BERTUZZO, CARMEN SILVIA; LEVY, CARLOS EMILIO; RIBEIRO, ANTONIO FERNANDO; RIBEIRO, JOSE DIRCEU. Hypertonic Saline as a Useful Tool for Sputum Induction and Pathogen Detection in Cystic Fibrosis. Lung, v. 195, n. 4, p. 431-439, . (11/18845-1, 15/12858-5, 11/12939-4, 15/12183-8)
ANDRESSA OLIVEIRA PEIXOTO; FERNANDO AUGUSTO LIMA MARSON; TIAGO HENRIQUE SOUZA; ANDREA DE MELO ALEXANDRE FRAGA; JOSÉ DIRCEU RIBEIRO. Lung ultrasound assessment of response to antibiotic therapy in cystic fibrosis exacerbations: a study of two cases. Jornal Brasileiro de Pneumologia, v. 45, n. 6, p. -, . (11/12939-4, 15/12183-8, 11/18845-1, 15/12858-5)
LUIZ, LIVIA COCATO; LIMA MARSON, FERNANDO AUGUSTO; BRESCIANI ALMEIDA, CELIZE CRUZ; DALBO CONTRERA TORO, ADYLEIA APARECIDA; NUCCI, ANAMARLI; RIBEIRO, JOSE DIRCEU. Analysis of motor and respiratory function in Duchenne muscular dystrophy patients. Respiratory Physiology & Neurobiology, v. 262, p. 1-11, . (11/18845-1, 15/12858-5, 11/12939-4, 15/12183-8)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MARSON, Fernando Augusto de Lima. Polymorphisms on key genes of the inflammatory response in allergic asthma, and their role in cystic fibrosis and severe acute viral bronchiolitis. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.

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