Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da FAMERP |
Texto Completo: | http://bdtd.famerp.br/handle/tede/398 |
Resumo: | Congenital heart defects (CHD) are present in approximately 40 to 60% of individuals with Down syndrome (DS). It is the leading cause of death in the first years of life in individuals with the syndrome. Polymorphisms in maternal and fetal genes encoding enzymes involved in folate metabolism have been associated with the development of congenital heart defects. Objectives: To assess if the presence of polymorphism (MTHFR rs4846048, MTHFR rs4846049, hsa-mir-149 rs2292832, MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, and SHMT C1420T) in individuals with DS is associated with the occurrence of CHD in these individuals. We also evaluated the association between maternal genetic polymorphisms MTHFR rs4846048, MTHFR rs4846049 and hsa-mir-149 rs2292832, and the presence of CHD in offspring with DS. Methods: This study included 139 individuals (80 individuals with DS and CHD, and 59 control subjects with DS without congenital heart disease). Molecular analysis of MTHFR rs4846048, MTHFR rs4846049 and hsa-mir-149 rs2292832 was carried out by real time polymerase chain reaction allelic discrimination. Genotyping data of MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, and SHMT C1420T were obtained from database of previous studies of the research group and also used to assess the risk for the occurrence of CHD in this study. Multiple logistic regression analyzes were performed to assess the risk of CHD in the presence of 17 polymorphisms in dominant and recessive genetic models. The median number of mutant alleles between groups was assessed by the Mann-Whitney test. Genotypic combination analysis was performed for the polymorphisms MTHFR rs4846048, MTHFR rs4846049, and hsa-mir-149 rs2292832, using Fisher's exact test, dominant model. Results: Multiple logistic regression analysis involving individuals with DS showed no association between 17 polymorphisms and the risk for CHD. The median number of polymorphic alleles did not differ among individuals with DS with and without CHD. On the other hand, the maternal genotypes hsa-mir-149 rs2292832 CT or TT were associated with reduced risk for isolated heart disease in the offspring (OR = 0,31; 95% CI = 0,13 to 0,72; P = 0,0063). The analysis of genotypic combinations of MTHFR rs4846048, MTHFR rs4846049, and hsa-mir-149 rs2292832 in individuals with DS, and their mothers showed no association between the different combinations and the risk for congenital heart disease. Conclusions: There is no evidence of association between the polymorphisms analyzed in individuals with DS and the occurrence of CHD. However, a lower risk of isolated congenital heart disease for individuals with DS is observed in the presence of maternal genotypes hsa-mir-149 rs2292832 CT or TT. |
id |
FMRP_b396085fd5c95cb327c60dd3d5db6916 |
---|---|
oai_identifier_str |
oai:localhost:tede/398 |
network_acronym_str |
FMRP |
network_name_str |
Biblioteca Digital de Teses e Dissertações da FAMERP |
repository_id_str |
4711 |
spelling |
Pavarino, Érika CristinaPérico, Joice Matos BiselliCastiglioni, LilianGalbiatti-Dias, Ana Lívia Silva39015079811http://lattes.cnpq.br/0053186279486560Santos, Mariana Fernanda2018-02-15T12:46:25Z2016-12-01Santos, Mariana Fernanda. Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down. 2016. 80 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto.1291http://bdtd.famerp.br/handle/tede/398Congenital heart defects (CHD) are present in approximately 40 to 60% of individuals with Down syndrome (DS). It is the leading cause of death in the first years of life in individuals with the syndrome. Polymorphisms in maternal and fetal genes encoding enzymes involved in folate metabolism have been associated with the development of congenital heart defects. Objectives: To assess if the presence of polymorphism (MTHFR rs4846048, MTHFR rs4846049, hsa-mir-149 rs2292832, MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, and SHMT C1420T) in individuals with DS is associated with the occurrence of CHD in these individuals. We also evaluated the association between maternal genetic polymorphisms MTHFR rs4846048, MTHFR rs4846049 and hsa-mir-149 rs2292832, and the presence of CHD in offspring with DS. Methods: This study included 139 individuals (80 individuals with DS and CHD, and 59 control subjects with DS without congenital heart disease). Molecular analysis of MTHFR rs4846048, MTHFR rs4846049 and hsa-mir-149 rs2292832 was carried out by real time polymerase chain reaction allelic discrimination. Genotyping data of MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, and SHMT C1420T were obtained from database of previous studies of the research group and also used to assess the risk for the occurrence of CHD in this study. Multiple logistic regression analyzes were performed to assess the risk of CHD in the presence of 17 polymorphisms in dominant and recessive genetic models. The median number of mutant alleles between groups was assessed by the Mann-Whitney test. Genotypic combination analysis was performed for the polymorphisms MTHFR rs4846048, MTHFR rs4846049, and hsa-mir-149 rs2292832, using Fisher's exact test, dominant model. Results: Multiple logistic regression analysis involving individuals with DS showed no association between 17 polymorphisms and the risk for CHD. The median number of polymorphic alleles did not differ among individuals with DS with and without CHD. On the other hand, the maternal genotypes hsa-mir-149 rs2292832 CT or TT were associated with reduced risk for isolated heart disease in the offspring (OR = 0,31; 95% CI = 0,13 to 0,72; P = 0,0063). The analysis of genotypic combinations of MTHFR rs4846048, MTHFR rs4846049, and hsa-mir-149 rs2292832 in individuals with DS, and their mothers showed no association between the different combinations and the risk for congenital heart disease. Conclusions: There is no evidence of association between the polymorphisms analyzed in individuals with DS and the occurrence of CHD. However, a lower risk of isolated congenital heart disease for individuals with DS is observed in the presence of maternal genotypes hsa-mir-149 rs2292832 CT or TT.Defeitos cardíacos congênitos (DCC) estão presentes em aproximadamente 40 a 60% dos indivíduos com a síndrome de Down (SD) e representam a principal causa de morte nos primeiros anos de vida em indivíduos com a síndrome. Polimorfismos em genes maternos e fetais, que codificam enzimas envolvidas no metabolismo do folato, têm sido associados com o desenvolvimento de cardiopatias congênitas. Objetivos: Avaliar se a presença dos polimorfismos MTHFR rs4846048, MTHFR rs4846049, hsa-mir-149 rs2292832, MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, SHMT C1420T em indivíduos com SD está associada com a ocorrência de DCC nesses indivíduos. Também foi avaliada a associação entre os polimorfismos genéticos maternos MTHFR rs4846048, MTHFR rs4846049 e hsa-mir-149 rs2292832 e a presença de DCC na prole com SD. Casuística e Método: Este estudo incluiu 139 indivíduos (80 indivíduos com SD e DCC e 59 indivíduos controles com SD, sem cardiopatia congênita). A análise molecular dos polimorfismos MTHFR rs4846048, MTHFR rs4846049 e hsa-mir-149 rs2292832 foi realizada pelo método discriminação alélica por meio de reação em cadeia da polimerase em tempo real. Os dados da genotipagem dos polimorfismos MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, SHMT C1420T foram obtidos de banco de dados de trabalhos previamente publicados pelo grupo de pesquisa e utilizados para avaliar o risco para a ocorrência de DCC no presente estudo. Análises de regressão logística múltipla foram realizadas para avaliar o risco de DCC na presença dos 17 polimorfismos nos modelos genéticos dominante e recessivo. A mediana do número de alelos mutantes entre os grupos foi avaliada pelo teste de Mann-Whitney. Análise de combinação genotípica foi realizada para os polimorfismos MTHFR rs4846048, MTHFR rs4846049 e hsa-mir-149 rs2292832, utilizando o teste exato de Fisher, no modelo dominante. Resultados: As análises de regressão logística múltipla, envolvendo os indivíduos com SD, não evidenciaram associação entre os 17 polimorfismos e o risco para DCC. A mediana do número de alelos polimórficos também não diferiu entre os indivíduos com SD com e sem DCC. Por outro lado, os genótipos maternos hsa-mir-149 rs2292832 CT ou TT foram associados ao risco reduzido para cardiopatia isolada na prole com SD (OR = 0,31; IC 95% = 0,13-0,72; P = 0,0063). A análise das combinações genotípicas dos polimorfismos MTHFR rs4846048, MTHFR rs4846049 e hsa-mir-149 rs2292832, nos indivíduos com SD e nas suas mães, não mostrou associação entre as diferentes combinações e o risco para cardiopatia congênita. Conclusões: Na casuística avaliada não há evidências de associação entre os polimorfismos analisados em indivíduos com SD e a ocorrência de DCC; entretanto um menor risco de cardiopatia congênita isolada para os indivíduos com SD é observado na presença dos genótipos maternos hsa-mir-149 rs2292832 CT ou TT.Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2018-02-15T12:46:24Z No. of bitstreams: 1 marianafernandadossantos_dissert.pdf: 1735247 bytes, checksum: 1bde0ab992e930a0190504964f47726e (MD5)Made available in DSpace on 2018-02-15T12:46:25Z (GMT). No. of bitstreams: 1 marianafernandadossantos_dissert.pdf: 1735247 bytes, checksum: 1bde0ab992e930a0190504964f47726e (MD5) Previous issue date: 2016-12-01Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP::6491868300948288337::600application/pdfporFaculdade de Medicina de São José do Rio PretoPrograma de Pós-Graduação em Ciências da Saúde::6954410853678806574::600FAMERPBrasilFaculdade 1::Departamento 1::306626487509624506::500Down SyndromePolymorphism, GeneticFolic AcidHeart Defects, CongenitalSíndrome de DownPolimorfismo GenéticoÁcido FólicoCardiopatias CongênitasCIENCIAS DA SAUDE::8765449414823306929::600Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Downinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da FAMERPinstname:Faculdade de Medicina de São José do Rio Preto (FAMERP)instacron:FAMERPLICENSElicense.txtlicense.txttext/plain; charset=utf-82165bd3efa91386c1718a7f26a329fdcb468MD51ORIGINALmarianafernandadossantos_dissert.pdfmarianafernandadossantos_dissert.pdfapplication/pdf17352471bde0ab992e930a0190504964f47726eMD52http://bdtd.famerp.br/bitstream/tede/398/1/license.txthttp://bdtd.famerp.br/bitstream/tede/398/2/marianafernandadossantos_dissert.pdftede/3982019-02-04 11:06:10.522oai:localhost: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Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.famerp.br/PUBhttps://bdtd.famerp.br/oai/requestsbdc@famerp.br||joao.junior@famerp.bropendoar:47112019-02-04T13:06:10Biblioteca Digital de Teses e Dissertações da FAMERP - Faculdade de Medicina de São José do Rio Preto (FAMERP)false |
dc.title.por.fl_str_mv |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down |
title |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down |
spellingShingle |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down Santos, Mariana Fernanda Down Syndrome Polymorphism, Genetic Folic Acid Heart Defects, Congenital Síndrome de Down Polimorfismo Genético Ácido Fólico Cardiopatias Congênitas CIENCIAS DA SAUDE::8765449414823306929::600 |
title_short |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down |
title_full |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down |
title_fullStr |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down |
title_full_unstemmed |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down |
title_sort |
Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down |
author |
Santos, Mariana Fernanda |
author_facet |
Santos, Mariana Fernanda |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Pavarino, Érika Cristina |
dc.contributor.advisor-co1.fl_str_mv |
Périco, Joice Matos Biselli |
dc.contributor.referee1.fl_str_mv |
Castiglioni, Lilian |
dc.contributor.referee2.fl_str_mv |
Galbiatti-Dias, Ana Lívia Silva |
dc.contributor.authorID.fl_str_mv |
39015079811 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0053186279486560 |
dc.contributor.author.fl_str_mv |
Santos, Mariana Fernanda |
contributor_str_mv |
Pavarino, Érika Cristina Périco, Joice Matos Biselli Castiglioni, Lilian Galbiatti-Dias, Ana Lívia Silva |
dc.subject.eng.fl_str_mv |
Down Syndrome Polymorphism, Genetic Folic Acid Heart Defects, Congenital |
topic |
Down Syndrome Polymorphism, Genetic Folic Acid Heart Defects, Congenital Síndrome de Down Polimorfismo Genético Ácido Fólico Cardiopatias Congênitas CIENCIAS DA SAUDE::8765449414823306929::600 |
dc.subject.por.fl_str_mv |
Síndrome de Down Polimorfismo Genético Ácido Fólico Cardiopatias Congênitas |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::8765449414823306929::600 |
description |
Congenital heart defects (CHD) are present in approximately 40 to 60% of individuals with Down syndrome (DS). It is the leading cause of death in the first years of life in individuals with the syndrome. Polymorphisms in maternal and fetal genes encoding enzymes involved in folate metabolism have been associated with the development of congenital heart defects. Objectives: To assess if the presence of polymorphism (MTHFR rs4846048, MTHFR rs4846049, hsa-mir-149 rs2292832, MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, and SHMT C1420T) in individuals with DS is associated with the occurrence of CHD in these individuals. We also evaluated the association between maternal genetic polymorphisms MTHFR rs4846048, MTHFR rs4846049 and hsa-mir-149 rs2292832, and the presence of CHD in offspring with DS. Methods: This study included 139 individuals (80 individuals with DS and CHD, and 59 control subjects with DS without congenital heart disease). Molecular analysis of MTHFR rs4846048, MTHFR rs4846049 and hsa-mir-149 rs2292832 was carried out by real time polymerase chain reaction allelic discrimination. Genotyping data of MTHFR C677T, MTHFR A1298C, MTHFR T1317C, MTR A2756G, MTRR A66G, SLC19A1 A80G, TC2 A67G, TC2 C776G, CßS 844ins68, CßS T833C, MTHFD1 G1958A, BHMT G742A, DHFR del 19 pb, and SHMT C1420T were obtained from database of previous studies of the research group and also used to assess the risk for the occurrence of CHD in this study. Multiple logistic regression analyzes were performed to assess the risk of CHD in the presence of 17 polymorphisms in dominant and recessive genetic models. The median number of mutant alleles between groups was assessed by the Mann-Whitney test. Genotypic combination analysis was performed for the polymorphisms MTHFR rs4846048, MTHFR rs4846049, and hsa-mir-149 rs2292832, using Fisher's exact test, dominant model. Results: Multiple logistic regression analysis involving individuals with DS showed no association between 17 polymorphisms and the risk for CHD. The median number of polymorphic alleles did not differ among individuals with DS with and without CHD. On the other hand, the maternal genotypes hsa-mir-149 rs2292832 CT or TT were associated with reduced risk for isolated heart disease in the offspring (OR = 0,31; 95% CI = 0,13 to 0,72; P = 0,0063). The analysis of genotypic combinations of MTHFR rs4846048, MTHFR rs4846049, and hsa-mir-149 rs2292832 in individuals with DS, and their mothers showed no association between the different combinations and the risk for congenital heart disease. Conclusions: There is no evidence of association between the polymorphisms analyzed in individuals with DS and the occurrence of CHD. However, a lower risk of isolated congenital heart disease for individuals with DS is observed in the presence of maternal genotypes hsa-mir-149 rs2292832 CT or TT. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-12-01 |
dc.date.accessioned.fl_str_mv |
2018-02-15T12:46:25Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Santos, Mariana Fernanda. Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down. 2016. 80 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto. |
dc.identifier.uri.fl_str_mv |
http://bdtd.famerp.br/handle/tede/398 |
dc.identifier.doi.por.fl_str_mv |
1291 |
identifier_str_mv |
Santos, Mariana Fernanda. Impacto de polimorfismos de genes do metabolismo do folato e do microRNA hsa-mir-149 no risco para cardiopatias congênitas em indivíduos com síndrome de Down. 2016. 80 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto. 1291 |
url |
http://bdtd.famerp.br/handle/tede/398 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Faculdade de Medicina de São José do Rio Preto |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências da Saúde::6954410853678806574::600 |
dc.publisher.initials.fl_str_mv |
FAMERP |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade 1::Departamento 1::306626487509624506::500 |
publisher.none.fl_str_mv |
Faculdade de Medicina de São José do Rio Preto |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da FAMERP instname:Faculdade de Medicina de São José do Rio Preto (FAMERP) instacron:FAMERP |
instname_str |
Faculdade de Medicina de São José do Rio Preto (FAMERP) |
instacron_str |
FAMERP |
institution |
FAMERP |
reponame_str |
Biblioteca Digital de Teses e Dissertações da FAMERP |
collection |
Biblioteca Digital de Teses e Dissertações da FAMERP |
bitstream.url.fl_str_mv |
http://bdtd.famerp.br/bitstream/tede/398/1/license.txt http://bdtd.famerp.br/bitstream/tede/398/2/marianafernandadossantos_dissert.pdf |
bitstream.checksum.fl_str_mv |
bd3efa91386c1718a7f26a329fdcb468 1bde0ab992e930a0190504964f47726e |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da FAMERP - Faculdade de Medicina de São José do Rio Preto (FAMERP) |
repository.mail.fl_str_mv |
sbdc@famerp.br||joao.junior@famerp.br |
_version_ |
1809113652622524416 |