Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents

Autores
Gemma, Carolina; Sookoian, Silvia Cristina; Dieuzeide, Guillermo; García, Silvia Isabel; Gianotti, Tomas Fernández; González, Claudio D.; Pirola, Carlos José
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: To explore whether DNA methylation of the mitochondrial transcription factor A (TFAM) promoter is associated with insulin resistance in a sample of adolescents with features of metabolic syndrome. Methods: The data and blood samples were collected from 122 adolescents out of a cross-sectional study of 934 high-school students. The population was divided into two groups: noninsulin resistance (NIR) and insulin resistance (IR). After bisulfite treatment of genomic DNA from peripheral leukocytes, we used methylation-specific polymerase chain reaction (PCR) to assess DNA methylation of three putative methylation target sites (CpG) in the TFAM promoter. Results: The ratio of the promoter methylated DNA/unmethylated DNA was 0.012+/-0.0009 (1.2% of alleles), and inversely correlated with the biochemical features of insulin resistance (plasma fasting insulin R: -0.26, p<0.004 and homeostasis model assessment (HOMA) index R: -0.27, p<0.002), and obesity (R: -0.27, p<0.002). Multiple regression analysis showed that the log-transformed HOMA index correlated with the status of promoter methylation of TFAM, independently of body mass index (BMI) Z score (beta: -0.33+/-0.094, p=0.00094). Finally, the TFAM promoter methylated DNA/unmethylated DNA ratio was found to be significantly associated with insulin resistance as dichotomous variable (NIR n=45, 0.014+/-0.002 and IR n=77, 0.011+/-0.001, respectively, p<0.016). Conclusion: Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents.
Fil: Gemma, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Dieuzeide, Guillermo. Centro de apoyo a la investigación de la Esclerosis Múltiple; Argentina
Fil: García, Silvia Isabel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Gianotti, Tomas Fernández. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: González, Claudio D.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Materia
METHYLATION
TFAM
INSULIN-RESISTANCE
ADOLESCENTS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/103132
Acceder
id CONICETDig_c6782566451a637ebb14bb4fdd3c8707
oai_identifier_str oai:ri.conicet.gov.ar:11336/103132
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescentsGemma, CarolinaSookoian, Silvia CristinaDieuzeide, GuillermoGarcía, Silvia IsabelGianotti, Tomas FernándezGonzález, Claudio D.Pirola, Carlos JoséMETHYLATIONTFAMINSULIN-RESISTANCEADOLESCENTShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Purpose: To explore whether DNA methylation of the mitochondrial transcription factor A (TFAM) promoter is associated with insulin resistance in a sample of adolescents with features of metabolic syndrome. Methods: The data and blood samples were collected from 122 adolescents out of a cross-sectional study of 934 high-school students. The population was divided into two groups: noninsulin resistance (NIR) and insulin resistance (IR). After bisulfite treatment of genomic DNA from peripheral leukocytes, we used methylation-specific polymerase chain reaction (PCR) to assess DNA methylation of three putative methylation target sites (CpG) in the TFAM promoter. Results: The ratio of the promoter methylated DNA/unmethylated DNA was 0.012+/-0.0009 (1.2% of alleles), and inversely correlated with the biochemical features of insulin resistance (plasma fasting insulin R: -0.26, p<0.004 and homeostasis model assessment (HOMA) index R: -0.27, p<0.002), and obesity (R: -0.27, p<0.002). Multiple regression analysis showed that the log-transformed HOMA index correlated with the status of promoter methylation of TFAM, independently of body mass index (BMI) Z score (beta: -0.33+/-0.094, p=0.00094). Finally, the TFAM promoter methylated DNA/unmethylated DNA ratio was found to be significantly associated with insulin resistance as dichotomous variable (NIR n=45, 0.014+/-0.002 and IR n=77, 0.011+/-0.001, respectively, p<0.016). Conclusion: Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents.Fil: Gemma, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Dieuzeide, Guillermo. Centro de apoyo a la investigación de la Esclerosis Múltiple; ArgentinaFil: García, Silvia Isabel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Gianotti, Tomas Fernández. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: González, Claudio D.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaAcademic Press Inc Elsevier Science2010-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103132Gemma, Carolina; Sookoian, Silvia Cristina; Dieuzeide, Guillermo; García, Silvia Isabel; Gianotti, Tomas Fernández; et al.; Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents; Academic Press Inc Elsevier Science; Molecular Genetics And Metabolism; 100; 1; 5-2010; 83-871096-7192CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgme.2010.02.004info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1096719210000521info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:30:08Zoai:ri.conicet.gov.ar:11336/103132instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:30:08.472CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
title Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
spellingShingle Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
Gemma, Carolina
METHYLATION
TFAM
INSULIN-RESISTANCE
ADOLESCENTS
title_short Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
title_full Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
title_fullStr Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
title_full_unstemmed Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
title_sort Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents
dc.creator.none.fl_str_mv Gemma, Carolina
Sookoian, Silvia Cristina
Dieuzeide, Guillermo
García, Silvia Isabel
Gianotti, Tomas Fernández
González, Claudio D.
Pirola, Carlos José
author Gemma, Carolina
author_facet Gemma, Carolina
Sookoian, Silvia Cristina
Dieuzeide, Guillermo
García, Silvia Isabel
Gianotti, Tomas Fernández
González, Claudio D.
Pirola, Carlos José
author_role author
author2 Sookoian, Silvia Cristina
Dieuzeide, Guillermo
García, Silvia Isabel
Gianotti, Tomas Fernández
González, Claudio D.
Pirola, Carlos José
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv METHYLATION
TFAM
INSULIN-RESISTANCE
ADOLESCENTS
topic METHYLATION
TFAM
INSULIN-RESISTANCE
ADOLESCENTS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: To explore whether DNA methylation of the mitochondrial transcription factor A (TFAM) promoter is associated with insulin resistance in a sample of adolescents with features of metabolic syndrome. Methods: The data and blood samples were collected from 122 adolescents out of a cross-sectional study of 934 high-school students. The population was divided into two groups: noninsulin resistance (NIR) and insulin resistance (IR). After bisulfite treatment of genomic DNA from peripheral leukocytes, we used methylation-specific polymerase chain reaction (PCR) to assess DNA methylation of three putative methylation target sites (CpG) in the TFAM promoter. Results: The ratio of the promoter methylated DNA/unmethylated DNA was 0.012+/-0.0009 (1.2% of alleles), and inversely correlated with the biochemical features of insulin resistance (plasma fasting insulin R: -0.26, p<0.004 and homeostasis model assessment (HOMA) index R: -0.27, p<0.002), and obesity (R: -0.27, p<0.002). Multiple regression analysis showed that the log-transformed HOMA index correlated with the status of promoter methylation of TFAM, independently of body mass index (BMI) Z score (beta: -0.33+/-0.094, p=0.00094). Finally, the TFAM promoter methylated DNA/unmethylated DNA ratio was found to be significantly associated with insulin resistance as dichotomous variable (NIR n=45, 0.014+/-0.002 and IR n=77, 0.011+/-0.001, respectively, p<0.016). Conclusion: Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents.
Fil: Gemma, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Dieuzeide, Guillermo. Centro de apoyo a la investigación de la Esclerosis Múltiple; Argentina
Fil: García, Silvia Isabel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Gianotti, Tomas Fernández. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: González, Claudio D.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
description Purpose: To explore whether DNA methylation of the mitochondrial transcription factor A (TFAM) promoter is associated with insulin resistance in a sample of adolescents with features of metabolic syndrome. Methods: The data and blood samples were collected from 122 adolescents out of a cross-sectional study of 934 high-school students. The population was divided into two groups: noninsulin resistance (NIR) and insulin resistance (IR). After bisulfite treatment of genomic DNA from peripheral leukocytes, we used methylation-specific polymerase chain reaction (PCR) to assess DNA methylation of three putative methylation target sites (CpG) in the TFAM promoter. Results: The ratio of the promoter methylated DNA/unmethylated DNA was 0.012+/-0.0009 (1.2% of alleles), and inversely correlated with the biochemical features of insulin resistance (plasma fasting insulin R: -0.26, p<0.004 and homeostasis model assessment (HOMA) index R: -0.27, p<0.002), and obesity (R: -0.27, p<0.002). Multiple regression analysis showed that the log-transformed HOMA index correlated with the status of promoter methylation of TFAM, independently of body mass index (BMI) Z score (beta: -0.33+/-0.094, p=0.00094). Finally, the TFAM promoter methylated DNA/unmethylated DNA ratio was found to be significantly associated with insulin resistance as dichotomous variable (NIR n=45, 0.014+/-0.002 and IR n=77, 0.011+/-0.001, respectively, p<0.016). Conclusion: Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents.
publishDate 2010
dc.date.none.fl_str_mv 2010-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/103132
Gemma, Carolina; Sookoian, Silvia Cristina; Dieuzeide, Guillermo; García, Silvia Isabel; Gianotti, Tomas Fernández; et al.; Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents; Academic Press Inc Elsevier Science; Molecular Genetics And Metabolism; 100; 1; 5-2010; 83-87
1096-7192
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103132
identifier_str_mv Gemma, Carolina; Sookoian, Silvia Cristina; Dieuzeide, Guillermo; García, Silvia Isabel; Gianotti, Tomas Fernández; et al.; Methylation of TFAM gene promoter in peripheral white blood cells is associated with insulin resistance in adolescents; Academic Press Inc Elsevier Science; Molecular Genetics And Metabolism; 100; 1; 5-2010; 83-87
1096-7192
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgme.2010.02.004
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1096719210000521
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846083439765225472
score 13.22299

Publicaciones similares