Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Gabriel, Marta Lúcia lattes
Orientador(a): Souza, Antônio Soares lattes
Banca de defesa: Regacini, Rodrigo lattes, Bizotto, Thais Santana Gastardelo lattes, Braga, Fernanda Del Campo Braojos lattes, Piatto, Vânia Belintani lattes
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Faculdade de Medicina de São José do Rio Preto
Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências da Saúde
Departamento: Faculdade 1::Departamento 1
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://bdtd.famerp.br/handle/tede/542
Resumo: Periventricular leukomalacia is a frequent consequence of hypoxic-ischemic injury. Functional cytokine gene variants that result in altered production of inflammatory (TNF-α, and IL-1β) or anti-inflammatory (IL-10) cytokines may modify disease processes, including periventricular leukomalacia. Objective: The aim of this study was to evaluate if there is a relationship between the two pro-inflammatory polymorphisms (TNF-α-1031T/C and IL-1β-511C/T) and the anti-inflammatory polymorphism IL-10-1082G/A and periventricular leukomalacia risk in newborns with and without this injury. Materials and methods: A case-control study performed at the Neonatal Intensive Care Unit of the Children's Hospital and Maternity of the SJRio Preto Medical School (FAMERP). Fifty preterm and term newborns were examined as index cases and 50 term newborns as controls, of both genders to both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed the three polymorphisms were amplified by Polimerase Chain Reaction-Restriction Fragment Lenght Polymorphism (PCR/RFLP). Results: Gestational age ranged from 25 to 39 weeks, in Case Group, and at Control Group it ranged from 38 to 42.5 weeks (p<0.0001). Statistically significant association was found between TNF-α-1031T/C high expression genotype TC (intermediate productor inflammatory cytokine) (OR, 2.495; 95% CI, 1.10-5.63; p=0.043) as well as between genotypes (TC+CC) (intermediate + high productors inflammatory cytokine) (OR, 2.471; 95% CI, 1.10-5.55; p=0.044) and risk of periventricular leukomalacia. Statistically significant association was found between IL-1β-511C/T high expression genotypes (CT+TT) intermediate + high productors inflammatory cytokine) (OR, 23.120; 95% CI, 1.31-409.4; p=0.003) and risk of periventricular leukomalacia. Statistically significant association between IL-10-1082G/A high expression genotype GG (anti-inflammatory cytokine high productor) (OR, 0.07407; 95% CI, 0.02-0.34; p<0.0001) as well as between IL-10-1082G high expression allele (OR, 0.5098; 95% CI, 0.29-0.91; p=0,030) and periventricular leukomalacia reduced risk was observed. There was a statistically significant association between TC/CT/GA genotypes combination and the risk of periventricular leukomalacia (OR, 6.469; 95% CI, 2.00-20.92; p=0.001). Conclusions: There is evidence of an association between the both TNF-α-1031T/C and IL-1β-511C/T inflammatory polymorphisms and periventricular leukomalacia risk, and an association of the IL-10-1082G/A anti-inflammatory polymorphism and periventricular leukomalacia reduced risk, in this studied newborns population.
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spelling Souza, Antônio Soareshttp://lattes.cnpq.br/1501466230111779Regacini, Rodrigo1192557620651923Bizotto, Thais Santana Gastardelohttp://lattes.cnpq.br/2055842801153417Braga, Fernanda Del Campo Braojoshttp://lattes.cnpq.br/5128875881346093Piatto, Vânia Belintanihttp://lattes.cnpq.br/623031373328870815933162833http://lattes.cnpq.br/5615061465603626Gabriel, Marta Lúcia2019-06-06T18:36:20Z2018-12-07Gabriel, Marta Lúcia. Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas. 2018. 69 f. Tese (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto.1409http://bdtd.famerp.br/handle/tede/542Periventricular leukomalacia is a frequent consequence of hypoxic-ischemic injury. Functional cytokine gene variants that result in altered production of inflammatory (TNF-α, and IL-1β) or anti-inflammatory (IL-10) cytokines may modify disease processes, including periventricular leukomalacia. Objective: The aim of this study was to evaluate if there is a relationship between the two pro-inflammatory polymorphisms (TNF-α-1031T/C and IL-1β-511C/T) and the anti-inflammatory polymorphism IL-10-1082G/A and periventricular leukomalacia risk in newborns with and without this injury. Materials and methods: A case-control study performed at the Neonatal Intensive Care Unit of the Children's Hospital and Maternity of the SJRio Preto Medical School (FAMERP). Fifty preterm and term newborns were examined as index cases and 50 term newborns as controls, of both genders to both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed the three polymorphisms were amplified by Polimerase Chain Reaction-Restriction Fragment Lenght Polymorphism (PCR/RFLP). Results: Gestational age ranged from 25 to 39 weeks, in Case Group, and at Control Group it ranged from 38 to 42.5 weeks (p<0.0001). Statistically significant association was found between TNF-α-1031T/C high expression genotype TC (intermediate productor inflammatory cytokine) (OR, 2.495; 95% CI, 1.10-5.63; p=0.043) as well as between genotypes (TC+CC) (intermediate + high productors inflammatory cytokine) (OR, 2.471; 95% CI, 1.10-5.55; p=0.044) and risk of periventricular leukomalacia. Statistically significant association was found between IL-1β-511C/T high expression genotypes (CT+TT) intermediate + high productors inflammatory cytokine) (OR, 23.120; 95% CI, 1.31-409.4; p=0.003) and risk of periventricular leukomalacia. Statistically significant association between IL-10-1082G/A high expression genotype GG (anti-inflammatory cytokine high productor) (OR, 0.07407; 95% CI, 0.02-0.34; p<0.0001) as well as between IL-10-1082G high expression allele (OR, 0.5098; 95% CI, 0.29-0.91; p=0,030) and periventricular leukomalacia reduced risk was observed. There was a statistically significant association between TC/CT/GA genotypes combination and the risk of periventricular leukomalacia (OR, 6.469; 95% CI, 2.00-20.92; p=0.001). Conclusions: There is evidence of an association between the both TNF-α-1031T/C and IL-1β-511C/T inflammatory polymorphisms and periventricular leukomalacia risk, and an association of the IL-10-1082G/A anti-inflammatory polymorphism and periventricular leukomalacia reduced risk, in this studied newborns population.A leucomalacia periventricular e uma consequencia frequente de lesoes hipoxico-isquemicas. Variantes funcionais dos genes das citocinas que resultam em producao alterada de citocinas inflamatorias (TNF-ƒ¿ e IL-1ƒÀ) ou anti-inflamatorias (IL-10) podem modificar a evolucao da doenca, incluindo a leucomalacia periventricular. Objetivos: Investigar a associacao entre ambos os polimorfismos inflamatorios (-1031T/C no gene TNF-ƒ¿ e -511C/T no gene IL-1ƒÀ) e o anti-inflamatorio (-1082G/A no gene IL-10) e o risco da leucomalacia periventricular em neonatos com e sem esta afeccao. Material e Metodos: Estudo de caso-controle realizado na Unidade de Terapia Intensiva do Hospital da Crianca e Maternidade da Faculdade Medicina de Sao Jose do Rio Preto (FAMERP). Cinquenta neonatos prematuros e a termo (Grupo Casos) e 50 neonatos a termo (Grupo Controle), de ambos os generos, foram incluidos. O DNA foi extraido de leucocitos de sangue periferico e os sitios que abrangem os tres polimorfismos foram amplificados pela Reacao em Cadeia da Polimerase/Analise de Restricao Enzimatica (PCR/RFLP). Resultados: A idade gestacional variou de 25 a 39 semanas no Grupo Casos e, no Grupo Controle, a idade gestacional variou de 38 a 42,5 semanas (p<0,0001). Foi encontrada associacao entre o genotipo TC (produtor intermediario de citocina inflamatoria) (OR, 2,495; 95% IC, 1,10-5,63; p=0,043) assim como entre os genotipos TC+CC (produtores inflamatorios intermediario+alto) (OR, 2,471; 95% IC, 1,10-5,55; p=0,044) no gene TNF-ƒ¿ e o risco de leucomalacia periventricular. Estatisticamente significante associacao foi encontrada entre os genotipos (CT+TT) (produtores inflamatorios intermediario+alto) (OR, 23,120; 95% IC, 1,31-409,4; p=0,003) no gene IL-1ƒÀ e o risco de leucomalacia periventricular. No gene IL-10, foi encontrada associacao significativa a menor risco de leucomalacia periventricular para o genotipo GG (alto produtor anti-inflamatorio) (OR, 0,07407; 95% IC, 0,02-0,34; p<0,0001) assim como para o alelo G (OR, 0,5098; 95% IC, 0,29-0,91; p=0,030). Houve associacao significativa entre a combinacao dos genotipos TC/CT/GA e o risco de leucomalacia periventricular (OR, 6,469; 95% CI, 2,00-20,92; p=0,001). Conclusao: Ha associacao entre os polimorfismos inflamatorios (-1031T/C no gene TNF-ƒ¿ e -511C/T no gene IL-1ƒÀ) e o risco de desenvolvimento de leucomalacia periventricular e associacao do polimorfismo anti-inflamatorio (-1082G/A no gene IL-10) ao menor risco de desenvolvimento da leucomalacia periventricular, na populacao de neonatos estudada.Submitted by Suzana Dias (suzana.dias@famerp.br) on 2019-06-06T18:36:20Z No. of bitstreams: 1 MartaLuciaGabriel_Tese.pdf: 1927999 bytes, checksum: 566f4aa78d7c0d81a0a2df2ddc854993 (MD5)Made available in DSpace on 2019-06-06T18:36:20Z (GMT). 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dc.title.por.fl_str_mv Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
title Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
spellingShingle Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
Gabriel, Marta Lúcia
Patogênese Homeopática
Polimorfismo Genético
Leucomalácia Periventricular
Interleucina-1
Pathogenesis, Homeopathic
Polymorphism, Genetic
Leukomalacia, Periventricular
Interleukin-1
CIENCIAS DA SAUDE
title_short Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
title_full Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
title_fullStr Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
title_full_unstemmed Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
title_sort Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas
author Gabriel, Marta Lúcia
author_facet Gabriel, Marta Lúcia
author_role author
dc.contributor.advisor1.fl_str_mv Souza, Antônio Soares
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1501466230111779
dc.contributor.referee1.fl_str_mv Regacini, Rodrigo
dc.contributor.referee1Lattes.fl_str_mv 1192557620651923
dc.contributor.referee2.fl_str_mv Bizotto, Thais Santana Gastardelo
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/2055842801153417
dc.contributor.referee3.fl_str_mv Braga, Fernanda Del Campo Braojos
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/5128875881346093
dc.contributor.referee4.fl_str_mv Piatto, Vânia Belintani
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/6230313733288708
dc.contributor.authorID.fl_str_mv 15933162833
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5615061465603626
dc.contributor.author.fl_str_mv Gabriel, Marta Lúcia
contributor_str_mv Souza, Antônio Soares
Regacini, Rodrigo
Bizotto, Thais Santana Gastardelo
Braga, Fernanda Del Campo Braojos
Piatto, Vânia Belintani
dc.subject.por.fl_str_mv Patogênese Homeopática
Polimorfismo Genético
Leucomalácia Periventricular
Interleucina-1
topic Patogênese Homeopática
Polimorfismo Genético
Leucomalácia Periventricular
Interleucina-1
Pathogenesis, Homeopathic
Polymorphism, Genetic
Leukomalacia, Periventricular
Interleukin-1
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv Pathogenesis, Homeopathic
Polymorphism, Genetic
Leukomalacia, Periventricular
Interleukin-1
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Periventricular leukomalacia is a frequent consequence of hypoxic-ischemic injury. Functional cytokine gene variants that result in altered production of inflammatory (TNF-α, and IL-1β) or anti-inflammatory (IL-10) cytokines may modify disease processes, including periventricular leukomalacia. Objective: The aim of this study was to evaluate if there is a relationship between the two pro-inflammatory polymorphisms (TNF-α-1031T/C and IL-1β-511C/T) and the anti-inflammatory polymorphism IL-10-1082G/A and periventricular leukomalacia risk in newborns with and without this injury. Materials and methods: A case-control study performed at the Neonatal Intensive Care Unit of the Children's Hospital and Maternity of the SJRio Preto Medical School (FAMERP). Fifty preterm and term newborns were examined as index cases and 50 term newborns as controls, of both genders to both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed the three polymorphisms were amplified by Polimerase Chain Reaction-Restriction Fragment Lenght Polymorphism (PCR/RFLP). Results: Gestational age ranged from 25 to 39 weeks, in Case Group, and at Control Group it ranged from 38 to 42.5 weeks (p<0.0001). Statistically significant association was found between TNF-α-1031T/C high expression genotype TC (intermediate productor inflammatory cytokine) (OR, 2.495; 95% CI, 1.10-5.63; p=0.043) as well as between genotypes (TC+CC) (intermediate + high productors inflammatory cytokine) (OR, 2.471; 95% CI, 1.10-5.55; p=0.044) and risk of periventricular leukomalacia. Statistically significant association was found between IL-1β-511C/T high expression genotypes (CT+TT) intermediate + high productors inflammatory cytokine) (OR, 23.120; 95% CI, 1.31-409.4; p=0.003) and risk of periventricular leukomalacia. Statistically significant association between IL-10-1082G/A high expression genotype GG (anti-inflammatory cytokine high productor) (OR, 0.07407; 95% CI, 0.02-0.34; p<0.0001) as well as between IL-10-1082G high expression allele (OR, 0.5098; 95% CI, 0.29-0.91; p=0,030) and periventricular leukomalacia reduced risk was observed. There was a statistically significant association between TC/CT/GA genotypes combination and the risk of periventricular leukomalacia (OR, 6.469; 95% CI, 2.00-20.92; p=0.001). Conclusions: There is evidence of an association between the both TNF-α-1031T/C and IL-1β-511C/T inflammatory polymorphisms and periventricular leukomalacia risk, and an association of the IL-10-1082G/A anti-inflammatory polymorphism and periventricular leukomalacia reduced risk, in this studied newborns population.
publishDate 2018
dc.date.issued.fl_str_mv 2018-12-07
dc.date.accessioned.fl_str_mv 2019-06-06T18:36:20Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv Gabriel, Marta Lúcia. Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas. 2018. 69 f. Tese (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/542
dc.identifier.doi.por.fl_str_mv 1409
identifier_str_mv Gabriel, Marta Lúcia. Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas. 2018. 69 f. Tese (Programa de Pós-Graduação em Ciências da Saúde) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto.
1409
url http://bdtd.famerp.br/handle/tede/542
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv -6954410853678806574
dc.relation.confidence.fl_str_mv 500
500
600
dc.relation.department.fl_str_mv 306626487509624506
dc.relation.cnpq.fl_str_mv 8765449414823306929
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
dc.publisher.initials.fl_str_mv FAMERP
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Faculdade 1::Departamento 1
publisher.none.fl_str_mv Faculdade de Medicina de São José do Rio Preto
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