A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity

Autores
Sookoian, Silvia Cristina; Castaño, Gustavo Osvaldo; Burgueño, Adriana Laura; Gianotti, Tomas Fernández; Rosselli, Maria Soledad; Pirola, Carlos José
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5–5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 × 10−5, adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% ± 3.9) in comparison with the CG genotype (26.3% ± 3.5) and GG genotype (33.3% ± 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (β 0.23 ± 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.
Fil: Sookoian, Silvia Cristina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
Fil: Castaño, Gustavo Osvaldo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
Fil: Burgueño, Adriana Laura. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gianotti, Tomas Fernández. Universidad de Buenos Aires; Argentina
Fil: Rosselli, Maria Soledad. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pirola, Carlos José. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
FATTY LIVER
GENETIC VARIANTS
PNPLA3
NASH
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:11336/103130
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/103130
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severitySookoian, Silvia CristinaCastaño, Gustavo OsvaldoBurgueño, Adriana LauraGianotti, Tomas FernándezRosselli, Maria SoledadPirola, Carlos JoséFATTY LIVERGENETIC VARIANTSPNPLA3NASHhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5–5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 × 10−5, adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% ± 3.9) in comparison with the CG genotype (26.3% ± 3.5) and GG genotype (33.3% ± 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (β 0.23 ± 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.Fil: Sookoian, Silvia Cristina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Castaño, Gustavo Osvaldo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Burgueño, Adriana Laura. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gianotti, Tomas Fernández. Universidad de Buenos Aires; ArgentinaFil: Rosselli, Maria Soledad. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pirola, Carlos José. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Society for Biochemistry and Molecular Biology2009-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103130Sookoian, Silvia Cristina; Castaño, Gustavo Osvaldo; Burgueño, Adriana Laura; Gianotti, Tomas Fernández; Rosselli, Maria Soledad; et al.; A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 50; 10; 10-2009; 2111-21160022-22751539-7262CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.P900013-JLR200info:eu-repo/semantics/altIdentifier/url/https://www.jlr.org/content/50/10/2111info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:36Zoai:ri.conicet.gov.ar:11336/103130instacron: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:34982025-09-29 09:59:36.239CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
title A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
spellingShingle A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
Sookoian, Silvia Cristina
FATTY LIVER
GENETIC VARIANTS
PNPLA3
NASH
title_short A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
title_full A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
title_fullStr A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
title_full_unstemmed A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
title_sort A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
dc.creator.none.fl_str_mv Sookoian, Silvia Cristina
Castaño, Gustavo Osvaldo
Burgueño, Adriana Laura
Gianotti, Tomas Fernández
Rosselli, Maria Soledad
Pirola, Carlos José
author Sookoian, Silvia Cristina
author_facet Sookoian, Silvia Cristina
Castaño, Gustavo Osvaldo
Burgueño, Adriana Laura
Gianotti, Tomas Fernández
Rosselli, Maria Soledad
Pirola, Carlos José
author_role author
author2 Castaño, Gustavo Osvaldo
Burgueño, Adriana Laura
Gianotti, Tomas Fernández
Rosselli, Maria Soledad
Pirola, Carlos José
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv FATTY LIVER
GENETIC VARIANTS
PNPLA3
NASH
topic FATTY LIVER
GENETIC VARIANTS
PNPLA3
NASH
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5–5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 × 10−5, adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% ± 3.9) in comparison with the CG genotype (26.3% ± 3.5) and GG genotype (33.3% ± 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (β 0.23 ± 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.
Fil: Sookoian, Silvia Cristina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
Fil: Castaño, Gustavo Osvaldo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
Fil: Burgueño, Adriana Laura. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gianotti, Tomas Fernández. Universidad de Buenos Aires; Argentina
Fil: Rosselli, Maria Soledad. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pirola, Carlos José. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5–5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 × 10−5, adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% ± 3.9) in comparison with the CG genotype (26.3% ± 3.5) and GG genotype (33.3% ± 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (β 0.23 ± 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.
publishDate 2009
dc.date.none.fl_str_mv 2009-10
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/11336/103130
Sookoian, Silvia Cristina; Castaño, Gustavo Osvaldo; Burgueño, Adriana Laura; Gianotti, Tomas Fernández; Rosselli, Maria Soledad; et al.; A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 50; 10; 10-2009; 2111-2116
0022-2275
1539-7262
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103130
identifier_str_mv Sookoian, Silvia Cristina; Castaño, Gustavo Osvaldo; Burgueño, Adriana Laura; Gianotti, Tomas Fernández; Rosselli, Maria Soledad; et al.; A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 50; 10; 10-2009; 2111-2116
0022-2275
1539-7262
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.P900013-JLR200
info:eu-repo/semantics/altIdentifier/url/https://www.jlr.org/content/50/10/2111
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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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