Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals

Autores
Sookoian, Silvia Cristina; Gemma, Carolina; Pirola, Carlos Jose
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) contributes to the regulation of a large fraction of liver and pancreatic islet transcriptomes. AIM: To evaluate the influence of HNF4α polymorphisms across the entire locus on the occurrence of type 2 diabetes (T2D) by means of a meta-analysis. METHODS: We evaluated haplotype block structure of HNF4α variants owing to linkage disequilibrium (LD). From 1455 reports, we evaluated 21 observational studies. RESULTS: Six haplotype blocks of LD were constructed with SNPs with r2 > 0.8; there were also 14 unlinked SNPs. Overall, we included 22,920 cases and 26.657 controls. Among 17 heterogeneous studies (21,881 cases and 24,915 controls), including 3 SNPs of P2 promoter region in block 1, we observed a significant association with T2D in fixed (OR 0.94, 95%CI: 0.905–0.975, p = 0.001) and random (OR 0.988, 95%CI: 0.880–0.948, p = 0.000012) model. Three homogeneous studies were evaluated in block 2 (2684 cases and 2059 controls), and a significant association with T2D was also observed: OR: 1.121, 95%CI 1.013–1.241, p = 0.027. Three additional variants were associated with T2D: two intronic SNPs (rs4810424: OR: 1.080, 95%CI: 1.010–1.154, p < 0.03 and rs3212183: OR: 0.843, 95%CI: 0.774–0.918, p < 0.00009) and one missense variant (rs1800961: OR: 0.770, 95%CI: 0.595–0.995, p < 0.05, 6562 cases and 6723 controls). Conclusions In addition to HNF4α variants in the promoter region, other SNPs may be involved on the occurrence of T2D.
Fil: Sookoian, Silvia Cristina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Gemma, Carolina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Pirola, Carlos Jose. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Materia
Gene Variants
Diabetes
Hnf4a
Genetic Risk
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/14973
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/14973
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individualsSookoian, Silvia CristinaGemma, CarolinaPirola, Carlos JoseGene VariantsDiabetesHnf4aGenetic Riskhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3BACKGROUND: The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) contributes to the regulation of a large fraction of liver and pancreatic islet transcriptomes. AIM: To evaluate the influence of HNF4α polymorphisms across the entire locus on the occurrence of type 2 diabetes (T2D) by means of a meta-analysis. METHODS: We evaluated haplotype block structure of HNF4α variants owing to linkage disequilibrium (LD). From 1455 reports, we evaluated 21 observational studies. RESULTS: Six haplotype blocks of LD were constructed with SNPs with r2 > 0.8; there were also 14 unlinked SNPs. Overall, we included 22,920 cases and 26.657 controls. Among 17 heterogeneous studies (21,881 cases and 24,915 controls), including 3 SNPs of P2 promoter region in block 1, we observed a significant association with T2D in fixed (OR 0.94, 95%CI: 0.905–0.975, p = 0.001) and random (OR 0.988, 95%CI: 0.880–0.948, p = 0.000012) model. Three homogeneous studies were evaluated in block 2 (2684 cases and 2059 controls), and a significant association with T2D was also observed: OR: 1.121, 95%CI 1.013–1.241, p = 0.027. Three additional variants were associated with T2D: two intronic SNPs (rs4810424: OR: 1.080, 95%CI: 1.010–1.154, p < 0.03 and rs3212183: OR: 0.843, 95%CI: 0.774–0.918, p < 0.00009) and one missense variant (rs1800961: OR: 0.770, 95%CI: 0.595–0.995, p < 0.05, 6562 cases and 6723 controls). Conclusions In addition to HNF4α variants in the promoter region, other SNPs may be involved on the occurrence of T2D.Fil: Sookoian, Silvia Cristina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Gemma, Carolina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Pirola, Carlos Jose. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaElsevier Inc2010-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14973Sookoian, Silvia Cristina; Gemma, Carolina; Pirola, Carlos Jose; Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals; Elsevier Inc; Molecular Genetics And Metabolism; 99; 1; 1-2010; 80-891096-7192enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S109671920900242Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgme.2009.08.004info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:21:21Zoai:ri.conicet.gov.ar:11336/14973instacron: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:34982025-09-10 13:21:21.69CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
title Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
spellingShingle Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
Sookoian, Silvia Cristina
Gene Variants
Diabetes
Hnf4a
Genetic Risk
title_short Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
title_full Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
title_fullStr Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
title_full_unstemmed Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
title_sort Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals
dc.creator.none.fl_str_mv Sookoian, Silvia Cristina
Gemma, Carolina
Pirola, Carlos Jose
author Sookoian, Silvia Cristina
author_facet Sookoian, Silvia Cristina
Gemma, Carolina
Pirola, Carlos Jose
author_role author
author2 Gemma, Carolina
Pirola, Carlos Jose
author2_role author
author
dc.subject.none.fl_str_mv Gene Variants
Diabetes
Hnf4a
Genetic Risk
topic Gene Variants
Diabetes
Hnf4a
Genetic Risk
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) contributes to the regulation of a large fraction of liver and pancreatic islet transcriptomes. AIM: To evaluate the influence of HNF4α polymorphisms across the entire locus on the occurrence of type 2 diabetes (T2D) by means of a meta-analysis. METHODS: We evaluated haplotype block structure of HNF4α variants owing to linkage disequilibrium (LD). From 1455 reports, we evaluated 21 observational studies. RESULTS: Six haplotype blocks of LD were constructed with SNPs with r2 > 0.8; there were also 14 unlinked SNPs. Overall, we included 22,920 cases and 26.657 controls. Among 17 heterogeneous studies (21,881 cases and 24,915 controls), including 3 SNPs of P2 promoter region in block 1, we observed a significant association with T2D in fixed (OR 0.94, 95%CI: 0.905–0.975, p = 0.001) and random (OR 0.988, 95%CI: 0.880–0.948, p = 0.000012) model. Three homogeneous studies were evaluated in block 2 (2684 cases and 2059 controls), and a significant association with T2D was also observed: OR: 1.121, 95%CI 1.013–1.241, p = 0.027. Three additional variants were associated with T2D: two intronic SNPs (rs4810424: OR: 1.080, 95%CI: 1.010–1.154, p < 0.03 and rs3212183: OR: 0.843, 95%CI: 0.774–0.918, p < 0.00009) and one missense variant (rs1800961: OR: 0.770, 95%CI: 0.595–0.995, p < 0.05, 6562 cases and 6723 controls). Conclusions In addition to HNF4α variants in the promoter region, other SNPs may be involved on the occurrence of T2D.
Fil: Sookoian, Silvia Cristina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Gemma, Carolina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Pirola, Carlos Jose. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
description BACKGROUND: The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) contributes to the regulation of a large fraction of liver and pancreatic islet transcriptomes. AIM: To evaluate the influence of HNF4α polymorphisms across the entire locus on the occurrence of type 2 diabetes (T2D) by means of a meta-analysis. METHODS: We evaluated haplotype block structure of HNF4α variants owing to linkage disequilibrium (LD). From 1455 reports, we evaluated 21 observational studies. RESULTS: Six haplotype blocks of LD were constructed with SNPs with r2 > 0.8; there were also 14 unlinked SNPs. Overall, we included 22,920 cases and 26.657 controls. Among 17 heterogeneous studies (21,881 cases and 24,915 controls), including 3 SNPs of P2 promoter region in block 1, we observed a significant association with T2D in fixed (OR 0.94, 95%CI: 0.905–0.975, p = 0.001) and random (OR 0.988, 95%CI: 0.880–0.948, p = 0.000012) model. Three homogeneous studies were evaluated in block 2 (2684 cases and 2059 controls), and a significant association with T2D was also observed: OR: 1.121, 95%CI 1.013–1.241, p = 0.027. Three additional variants were associated with T2D: two intronic SNPs (rs4810424: OR: 1.080, 95%CI: 1.010–1.154, p < 0.03 and rs3212183: OR: 0.843, 95%CI: 0.774–0.918, p < 0.00009) and one missense variant (rs1800961: OR: 0.770, 95%CI: 0.595–0.995, p < 0.05, 6562 cases and 6723 controls). Conclusions In addition to HNF4α variants in the promoter region, other SNPs may be involved on the occurrence of T2D.
publishDate 2010
dc.date.none.fl_str_mv 2010-01
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/11336/14973
Sookoian, Silvia Cristina; Gemma, Carolina; Pirola, Carlos Jose; Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals; Elsevier Inc; Molecular Genetics And Metabolism; 99; 1; 1-2010; 80-89
1096-7192
url http://hdl.handle.net/11336/14973
identifier_str_mv Sookoian, Silvia Cristina; Gemma, Carolina; Pirola, Carlos Jose; Influence of hepatocyte nuclear factor 4α (HNF4α) gene variants on the risk of type 2 diabetes: a meta-analysis in 49,577 individuals; Elsevier Inc; Molecular Genetics And Metabolism; 99; 1; 1-2010; 80-89
1096-7192
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S109671920900242X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgme.2009.08.004
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc
publisher.none.fl_str_mv Elsevier Inc
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
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