Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/17655 |
Resumo: | The knowledge of the determinants of vitamin D status in pregnant women is particularly important due to the potential implications of its insufficiency for both maternal and fetal health. In addition to sociodemographic and lifestyle factors, it is possible that single nucleotide polymorphisms (SNPs) determine the genetic predisposition of pregnant women to inadequate vitamin D status. Pregnancy is associated with important changes in vitamin D metabolism. Vitamin D status assessment in pregnant women based exclusively on the serum concentrations of the conventional vitamin D indicator [25(OH)D] has been questioned. In the present thesis, two original manuscripts are presented investigating a broad set of biomarkers of nutritional vitamin D status in Brazilian pregnant women and their demographic and lifestyle determinants (manuscript 1), as well as the association between concentrations of these biomarkers and SNPs the gene encoding vitamin D binding protein (DBP - GC gene) (manuscript 2). This is a cross-sectional study with a convenience sample (n = 123) conducted in women in the third trimester of pregnancy attended at a public maternity of the Municipal health in Rio de Janeiro, Brazil. Information on maternal age, educational attainment, gestational age, pre-gestational BMI, number of previous pregnancies, smoking habit, drinking habits and practicing of physical exercise during pregnancy were self-reported at the time of the interview. The skin pigmentation was evaluated using a portable colorimeter. Serum concentration of total 25(OH)D3 was measured by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Serum concentrations of albumin, DBP and PTH were determined. Free and bioavailable fractions of 25(OH)D3 were indirectly estimated based on the protein-ligand binding kinetics. The genotyping of the SNPs rs2282679 (G>T), rs4588 (G>T) e rs7041 (A>C) were performed by Real-Time PCR. In the first manuscript, using multiple linear regression analysis, gestational age was inversely associated with 25(OH)D3 concentrations, whereas pre-pregnancy BMI was directly associated with DBP concentrations (β = 5.84, 95% CI: 0.62, 11.06). Lower concentrations of 25(OH)D3, DBP and free and bioavailable 25(OH)D3 fractions were observed in women who had blood collected during the winter and autumn. In the second manuscript, after adjustments for season, gestational age and pre-pregnancy BMI, women with GG genotype (rs2282679) had lower DBP concentrations compared to those with TT genotype. The genotypes GT and GG (rs2282679) were associated with the highest PTH concentrations (β = 14.53, 95% CI: 3.86, 25.20 and β = 19.66, 95% CI: 0.28, 39, 04), while lower concentrations of PTH were observed in women with GT and TT genotypes at the SNP rs4588 (β = -14.12; 95% CI: -25.47, -2.78 and β = -19.39; 95% CI: -38.88, 0.11, respectively). Our results suggest that the season of the year, gestational age and pre-pregnancy BMI are the main factors determining the predisposition of pregnant women to vitamin D insufficiency and that, apparently, total 25(OH)D3, as well as its free and bioavailable fractions, provide similar information about vitamin D status in Brazilian pregnant women. The results also suggest that although the evaluated SNPs were not associated with 25(OH)D3 (both total and fractions), it appears that they may influence PTH concentrations, considered a marker of vitamin D function. |
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Bezerra, Flávia Fiorucihttp://lattes.cnpq.br/1523963949057333Reis, Marta Citelli doshttp://lattes.cnpq.br/1136248028072284Melo, Maria Eduarda Leão Diogeneshttp://lattes.cnpq.br/9949075350374241Pedrosa, Lucia de Fátima Camposhttp://lattes.cnpq.br/1863589790139155Zembrzuski, Verônica Marqueshttp://lattes.cnpq.br/7646216219999997http://lattes.cnpq.br/0282669959921778Pereira, Joana de Novaisjoanadenovais.nutri@gmail.com2022-04-29T16:26:13Z2019-07-26PEREIRA, Joana de Novais. Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos. 2019. 113 f. Tese (Doutorado em Alimentação, Nutrição e Saúde) - Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2019.http://www.bdtd.uerj.br/handle/1/17655The knowledge of the determinants of vitamin D status in pregnant women is particularly important due to the potential implications of its insufficiency for both maternal and fetal health. In addition to sociodemographic and lifestyle factors, it is possible that single nucleotide polymorphisms (SNPs) determine the genetic predisposition of pregnant women to inadequate vitamin D status. Pregnancy is associated with important changes in vitamin D metabolism. Vitamin D status assessment in pregnant women based exclusively on the serum concentrations of the conventional vitamin D indicator [25(OH)D] has been questioned. In the present thesis, two original manuscripts are presented investigating a broad set of biomarkers of nutritional vitamin D status in Brazilian pregnant women and their demographic and lifestyle determinants (manuscript 1), as well as the association between concentrations of these biomarkers and SNPs the gene encoding vitamin D binding protein (DBP - GC gene) (manuscript 2). This is a cross-sectional study with a convenience sample (n = 123) conducted in women in the third trimester of pregnancy attended at a public maternity of the Municipal health in Rio de Janeiro, Brazil. Information on maternal age, educational attainment, gestational age, pre-gestational BMI, number of previous pregnancies, smoking habit, drinking habits and practicing of physical exercise during pregnancy were self-reported at the time of the interview. The skin pigmentation was evaluated using a portable colorimeter. Serum concentration of total 25(OH)D3 was measured by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Serum concentrations of albumin, DBP and PTH were determined. Free and bioavailable fractions of 25(OH)D3 were indirectly estimated based on the protein-ligand binding kinetics. The genotyping of the SNPs rs2282679 (G>T), rs4588 (G>T) e rs7041 (A>C) were performed by Real-Time PCR. In the first manuscript, using multiple linear regression analysis, gestational age was inversely associated with 25(OH)D3 concentrations, whereas pre-pregnancy BMI was directly associated with DBP concentrations (β = 5.84, 95% CI: 0.62, 11.06). Lower concentrations of 25(OH)D3, DBP and free and bioavailable 25(OH)D3 fractions were observed in women who had blood collected during the winter and autumn. In the second manuscript, after adjustments for season, gestational age and pre-pregnancy BMI, women with GG genotype (rs2282679) had lower DBP concentrations compared to those with TT genotype. The genotypes GT and GG (rs2282679) were associated with the highest PTH concentrations (β = 14.53, 95% CI: 3.86, 25.20 and β = 19.66, 95% CI: 0.28, 39, 04), while lower concentrations of PTH were observed in women with GT and TT genotypes at the SNP rs4588 (β = -14.12; 95% CI: -25.47, -2.78 and β = -19.39; 95% CI: -38.88, 0.11, respectively). Our results suggest that the season of the year, gestational age and pre-pregnancy BMI are the main factors determining the predisposition of pregnant women to vitamin D insufficiency and that, apparently, total 25(OH)D3, as well as its free and bioavailable fractions, provide similar information about vitamin D status in Brazilian pregnant women. The results also suggest that although the evaluated SNPs were not associated with 25(OH)D3 (both total and fractions), it appears that they may influence PTH concentrations, considered a marker of vitamin D function.O conhecimento dos determinantes do estado de vitamina D em mulheres durante o período gestacional é particularmente importante devido as potenciais implicações da insuficiência dessa vitamina para a saúde materna e fetal. Além de fatores sociodemográficos e de estilo de vida, é possível que polimorfismos de nucleotídeos únicos (SNPs) determinem a predisposição de gestantes à inadequação de vitamina D. Por ser um período de importantes alterações no metabolismo da vitamina D, a determinação do estado dessa vitamina em gestantes baseada exclusivamente nas concentrações séricas do indicador convencional de adequação [25(OH)D] tem sido questionada. Na presente Tese são apresentados dois manuscritos originais que objetivaram investigar um amplo conjunto de biomarcadores de estado nutricional de vitamina D em gestantes brasileiras e seus determinantes demográficos e de estilo de vida (artigo 1), bem como a associação entre as concentrações desses biomarcadores e SNPs localizados no gene que codifica a proteína ligante de vitamina D (DBP - gene GC) (artigo 2). Trata-se de um estudo transversal com uma amostra de conveniência (n=123) composta por mulheres adultas no terceiro trimestre de gestação atendidas em uma maternidade pública da rede Municipal de saúde da cidade do Rio de Janeiro. Informações sobre idade materna, escolaridade, idade gestacional, IMC pré-gestacional, número de gestações anteriores, hábito de fumar, hábito de beber e de praticar atividade física durante a gestação foram autorrelatadas no momento da entrevista. A determinação da pigmentação da pele foi avaliada com auxílio de um colorímetro portátil. As concentrações séricas de 25(OH)D3 foram determinadas por Cromatografia Liquida de Alta Eficiência acoplada a um Detector de Arranjo de Diodos (CLAE-DAD). As concentrações séricas de albumina, DBP e PTH foram determinadas utilizando métodos convencionais. As frações livre e biodisponível de 25(OH)D3 foram determinadas indiretamente por equação matemática baseada na constante de afinidade de ligação com albumina e DBP. As genotipagens dos SNPs rs2282679 (G>T), rs4588 (G>T) e rs7041 (A>C) foram realizadas por PCR em tempo real. No primeiro artigo, utilizando análises de regressão linear múltipla, a idade gestacional se associou inversamente às concentrações de 25(OH)D3, enquanto o IMC-pré gestacional foi diretamente associado às concentrações de DBP (β = 5,84, 95% IC: 0,62, 11,06). As mulheres que tiveram o sangue coletado durante o inverno e o outono apresentaram menores concentrações de 25(OH)D3, DBP, 25(OH)D3 livre e 25(OH)D3 biodisponível. No segundo artigo, após ajustes pela estação do ano, idade gestacional e IMC pré-gestacional, as mulheres com o genótipo GG (rs2282679) apresentaram menores concentrações de DBP comparadas àquelas com genótipo TT. Os genótipos GT e GG (rs2282679) foram associados as maiores concentrações de PTH (β = 14,53; 95% IC: 3,86, 25,20 e β = 19,66; 95% IC: 0,28, 39,04), enquanto menores concentrações de PTH foram observadas nas mulheres com os genótipos GT e TT no SNP rs4588 (β = -14,12; 95% IC: -25,47, -2,78 e β = -19,39; 95% IC: -38,88, 0,11, respectivamente). Em conjunto, nossos resultados sugerem que a estação do ano, a idade gestacional, e o IMC pré-gestacional são os principais fatores responsáveis por determinar a predisposição de gestantes à insuficiência de vitamina D e que, aparentemente, as concentrações de 25(OH)D3 total e de suas frações livre e biodisponível fornecem informações semelhantes a respeito do estado nutricional de vitamina D em gestantes brasileiras. Os resultados sugerem ainda que os SNPs avaliados, embora não tenham apresentado associação com as concentrações de 25(OH)D3 total e frações, parecem influenciar as concentrações de PTH, considerado um indicador de funcionalidade da vitamina D.Submitted by Mariangela CEH/A (marianfig@gmail.com) on 2022-04-29T16:26:13Z No. of bitstreams: 2 Tese - Joana de Novais Pereira - 2019 - Completa.pdf: 2372156 bytes, checksum: 27557acb783f1680efa4ea9b96a6d3c3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2022-04-29T16:26:13Z (GMT). No. of bitstreams: 2 Tese - Joana de Novais Pereira - 2019 - Completa.pdf: 2372156 bytes, checksum: 27557acb783f1680efa4ea9b96a6d3c3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2019-07-26Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Alimentação, Nutrição e SaúdeUERJBrasilCentro Biomédico::Instituto de Nutriçãohttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessPregnancyVitamin DDemographic determinantsBrazilNutriçãoGestaçãoVitamina DDeterminantes demográficosSNPBrasilCIENCIAS DA SAUDE::NUTRICAOInvestigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticosInvestigation of biomarkers of vitamin D status in pregnant women and their sociodemographic, lifestyle and genetic determinantsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTese - Joana de Novais Pereira - 2019 - Completa.pdfTese - Joana de Novais Pereira - 2019 - Completa.pdfapplication/pdf2372156http://www.bdtd.uerj.br/bitstream/1/17655/5/Tese+-+Joana+de+Novais+Pereira+-+2019+-+Completa.pdf27557acb783f1680efa4ea9b96a6d3c3MD55CC-LICENSElicense_urllicense_urltext/plain; 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dc.title.por.fl_str_mv |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos |
dc.title.alternative.eng.fl_str_mv |
Investigation of biomarkers of vitamin D status in pregnant women and their sociodemographic, lifestyle and genetic determinants |
title |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos |
spellingShingle |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos Pereira, Joana de Novais Pregnancy Vitamin D Demographic determinants Brazil Nutrição Gestação Vitamina D Determinantes demográficos SNP Brasil CIENCIAS DA SAUDE::NUTRICAO |
title_short |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos |
title_full |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos |
title_fullStr |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos |
title_full_unstemmed |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos |
title_sort |
Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos |
author |
Pereira, Joana de Novais |
author_facet |
Pereira, Joana de Novais joanadenovais.nutri@gmail.com |
author_role |
author |
author2 |
joanadenovais.nutri@gmail.com |
author2_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bezerra, Flávia Fioruci |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1523963949057333 |
dc.contributor.referee1.fl_str_mv |
Reis, Marta Citelli dos |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/1136248028072284 |
dc.contributor.referee2.fl_str_mv |
Melo, Maria Eduarda Leão Diogenes |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/9949075350374241 |
dc.contributor.referee3.fl_str_mv |
Pedrosa, Lucia de Fátima Campos |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/1863589790139155 |
dc.contributor.referee4.fl_str_mv |
Zembrzuski, Verônica Marques |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/7646216219999997 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0282669959921778 |
dc.contributor.author.fl_str_mv |
Pereira, Joana de Novais joanadenovais.nutri@gmail.com |
contributor_str_mv |
Bezerra, Flávia Fioruci Reis, Marta Citelli dos Melo, Maria Eduarda Leão Diogenes Pedrosa, Lucia de Fátima Campos Zembrzuski, Verônica Marques |
dc.subject.eng.fl_str_mv |
Pregnancy Vitamin D Demographic determinants Brazil |
topic |
Pregnancy Vitamin D Demographic determinants Brazil Nutrição Gestação Vitamina D Determinantes demográficos SNP Brasil CIENCIAS DA SAUDE::NUTRICAO |
dc.subject.por.fl_str_mv |
Nutrição Gestação Vitamina D Determinantes demográficos SNP Brasil |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::NUTRICAO |
description |
The knowledge of the determinants of vitamin D status in pregnant women is particularly important due to the potential implications of its insufficiency for both maternal and fetal health. In addition to sociodemographic and lifestyle factors, it is possible that single nucleotide polymorphisms (SNPs) determine the genetic predisposition of pregnant women to inadequate vitamin D status. Pregnancy is associated with important changes in vitamin D metabolism. Vitamin D status assessment in pregnant women based exclusively on the serum concentrations of the conventional vitamin D indicator [25(OH)D] has been questioned. In the present thesis, two original manuscripts are presented investigating a broad set of biomarkers of nutritional vitamin D status in Brazilian pregnant women and their demographic and lifestyle determinants (manuscript 1), as well as the association between concentrations of these biomarkers and SNPs the gene encoding vitamin D binding protein (DBP - GC gene) (manuscript 2). This is a cross-sectional study with a convenience sample (n = 123) conducted in women in the third trimester of pregnancy attended at a public maternity of the Municipal health in Rio de Janeiro, Brazil. Information on maternal age, educational attainment, gestational age, pre-gestational BMI, number of previous pregnancies, smoking habit, drinking habits and practicing of physical exercise during pregnancy were self-reported at the time of the interview. The skin pigmentation was evaluated using a portable colorimeter. Serum concentration of total 25(OH)D3 was measured by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Serum concentrations of albumin, DBP and PTH were determined. Free and bioavailable fractions of 25(OH)D3 were indirectly estimated based on the protein-ligand binding kinetics. The genotyping of the SNPs rs2282679 (G>T), rs4588 (G>T) e rs7041 (A>C) were performed by Real-Time PCR. In the first manuscript, using multiple linear regression analysis, gestational age was inversely associated with 25(OH)D3 concentrations, whereas pre-pregnancy BMI was directly associated with DBP concentrations (β = 5.84, 95% CI: 0.62, 11.06). Lower concentrations of 25(OH)D3, DBP and free and bioavailable 25(OH)D3 fractions were observed in women who had blood collected during the winter and autumn. In the second manuscript, after adjustments for season, gestational age and pre-pregnancy BMI, women with GG genotype (rs2282679) had lower DBP concentrations compared to those with TT genotype. The genotypes GT and GG (rs2282679) were associated with the highest PTH concentrations (β = 14.53, 95% CI: 3.86, 25.20 and β = 19.66, 95% CI: 0.28, 39, 04), while lower concentrations of PTH were observed in women with GT and TT genotypes at the SNP rs4588 (β = -14.12; 95% CI: -25.47, -2.78 and β = -19.39; 95% CI: -38.88, 0.11, respectively). Our results suggest that the season of the year, gestational age and pre-pregnancy BMI are the main factors determining the predisposition of pregnant women to vitamin D insufficiency and that, apparently, total 25(OH)D3, as well as its free and bioavailable fractions, provide similar information about vitamin D status in Brazilian pregnant women. The results also suggest that although the evaluated SNPs were not associated with 25(OH)D3 (both total and fractions), it appears that they may influence PTH concentrations, considered a marker of vitamin D function. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-07-26 |
dc.date.accessioned.fl_str_mv |
2022-04-29T16:26:13Z |
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 |
PEREIRA, Joana de Novais. Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos. 2019. 113 f. Tese (Doutorado em Alimentação, Nutrição e Saúde) - Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2019. |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/17655 |
identifier_str_mv |
PEREIRA, Joana de Novais. Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos. 2019. 113 f. Tese (Doutorado em Alimentação, Nutrição e Saúde) - Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2019. |
url |
http://www.bdtd.uerj.br/handle/1/17655 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Alimentação, Nutrição e Saúde |
dc.publisher.initials.fl_str_mv |
UERJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Instituto de Nutrição |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UERJ instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
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Universidade do Estado do Rio de Janeiro (UERJ) |
instacron_str |
UERJ |
institution |
UERJ |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UERJ |
collection |
Biblioteca Digital de Teses e Dissertações da UERJ |
bitstream.url.fl_str_mv |
http://www.bdtd.uerj.br/bitstream/1/17655/5/Tese+-+Joana+de+Novais+Pereira+-+2019+-+Completa.pdf http://www.bdtd.uerj.br/bitstream/1/17655/2/license_url http://www.bdtd.uerj.br/bitstream/1/17655/3/license_text http://www.bdtd.uerj.br/bitstream/1/17655/4/license_rdf http://www.bdtd.uerj.br/bitstream/1/17655/1/license.txt |
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repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
repository.mail.fl_str_mv |
bdtd.suporte@uerj.br |
_version_ |
1811728709782077440 |