Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease

Autores
Pirola, Carlos José; Garaycoechea, Martin; Flichman, Diego Martin; Arrese, Marco; San Martino, Julio; Gazzi, Carla; Casta&ntildeo, Gustavo O; Sookoian, Silvia Cristina
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567 genotypes and the hepatic transcriptome. The A-INS allele protected against NAFLD [odds ratio (OR) per adenine allele = 0.667; 95% CI, 0.486−0.916; P = 0.012]; this effect was nonsignificant when logistic regression analysis included BMI. The A-INS allele protected against nonalcoholic steatohepatitis (NASH) (OR = 0.612; 95% CI, 0.388−0.964; P = 0.033), ballooning degeneration (OR = 0.474; 95% CI, 0.267−0.842; P = 0.01), lobular inflammation (OR = 0.475; 95% CI, 0.275−0.821; P = 0.007), and fibrosis (OR = 0.590; 95% CI, 0.361−0.965; P = 0.035). In patients carrying A-INS, HSD17B13 levels decreased proportionally to allele dosage. Whole-transcriptome genotype profiling showed overrepresented immune response-related pathways. Thus, the rs72613567 A-INS allele reduces the risk of NASH and progressive liver damage and may become a therapeutic target.
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Garaycoechea, Martin. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina
Fil: Arrese, Marco. Pontificia Universidad Católica de Chile; Chile
Fil: San Martino, Julio. Hospital Diego Thompson; Argentina
Fil: Gazzi, Carla. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Castaño, Gustavo O. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Materia
CIRRHOSIS
FIBROSIS
GENETICS
HERITABILITY
HYDROXYSTEROID 17- DEHYDROGENASE 13
MUTATIONS
NONALCOHOLIC STEATOHEPATITIS
PROTECTION
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:11336/94156
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/94156
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver diseasePirola, Carlos JoséGaraycoechea, MartinFlichman, Diego MartinArrese, MarcoSan Martino, JulioGazzi, CarlaCasta&ntildeo, Gustavo OSookoian, Silvia CristinaCIRRHOSISFIBROSISGENETICSHERITABILITYHYDROXYSTEROID 17- DEHYDROGENASE 13MUTATIONSNONALCOHOLIC STEATOHEPATITISPROTECTIONhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567 genotypes and the hepatic transcriptome. The A-INS allele protected against NAFLD [odds ratio (OR) per adenine allele = 0.667; 95% CI, 0.486−0.916; P = 0.012]; this effect was nonsignificant when logistic regression analysis included BMI. The A-INS allele protected against nonalcoholic steatohepatitis (NASH) (OR = 0.612; 95% CI, 0.388−0.964; P = 0.033), ballooning degeneration (OR = 0.474; 95% CI, 0.267−0.842; P = 0.01), lobular inflammation (OR = 0.475; 95% CI, 0.275−0.821; P = 0.007), and fibrosis (OR = 0.590; 95% CI, 0.361−0.965; P = 0.035). In patients carrying A-INS, HSD17B13 levels decreased proportionally to allele dosage. Whole-transcriptome genotype profiling showed overrepresented immune response-related pathways. Thus, the rs72613567 A-INS allele reduces the risk of NASH and progressive liver damage and may become a therapeutic target.Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Garaycoechea, Martin. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Arrese, Marco. Pontificia Universidad Católica de Chile; ChileFil: San Martino, Julio. Hospital Diego Thompson; ArgentinaFil: Gazzi, Carla. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Casta&ntildeo, Gustavo O. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaAmerican Society for Biochemistry and Molecular Biology2018-10info: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/11336/94156Pirola, Carlos José; Garaycoechea, Martin; Flichman, Diego Martin; Arrese, Marco; San Martino, Julio; et al.; Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 60; 1; 10-2018; 176-1850022-22751539-7262CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jlr.org/lookup/doi/10.1194/jlr.P089953info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.P089953info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:50Zoai:ri.conicet.gov.ar:11336/94156instacron: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:34982025-09-03 10:10:50.338CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
title Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
spellingShingle Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
Pirola, Carlos José
CIRRHOSIS
FIBROSIS
GENETICS
HERITABILITY
HYDROXYSTEROID 17- DEHYDROGENASE 13
MUTATIONS
NONALCOHOLIC STEATOHEPATITIS
PROTECTION
title_short Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
title_full Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
title_fullStr Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
title_full_unstemmed Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
title_sort Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease
dc.creator.none.fl_str_mv Pirola, Carlos José
Garaycoechea, Martin
Flichman, Diego Martin
Arrese, Marco
San Martino, Julio
Gazzi, Carla
Casta&ntildeo, Gustavo O
Sookoian, Silvia Cristina
author Pirola, Carlos José
author_facet Pirola, Carlos José
Garaycoechea, Martin
Flichman, Diego Martin
Arrese, Marco
San Martino, Julio
Gazzi, Carla
Casta&ntildeo, Gustavo O
Sookoian, Silvia Cristina
author_role author
author2 Garaycoechea, Martin
Flichman, Diego Martin
Arrese, Marco
San Martino, Julio
Gazzi, Carla
Casta&ntildeo, Gustavo O
Sookoian, Silvia Cristina
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CIRRHOSIS
FIBROSIS
GENETICS
HERITABILITY
HYDROXYSTEROID 17- DEHYDROGENASE 13
MUTATIONS
NONALCOHOLIC STEATOHEPATITIS
PROTECTION
topic CIRRHOSIS
FIBROSIS
GENETICS
HERITABILITY
HYDROXYSTEROID 17- DEHYDROGENASE 13
MUTATIONS
NONALCOHOLIC STEATOHEPATITIS
PROTECTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567 genotypes and the hepatic transcriptome. The A-INS allele protected against NAFLD [odds ratio (OR) per adenine allele = 0.667; 95% CI, 0.486−0.916; P = 0.012]; this effect was nonsignificant when logistic regression analysis included BMI. The A-INS allele protected against nonalcoholic steatohepatitis (NASH) (OR = 0.612; 95% CI, 0.388−0.964; P = 0.033), ballooning degeneration (OR = 0.474; 95% CI, 0.267−0.842; P = 0.01), lobular inflammation (OR = 0.475; 95% CI, 0.275−0.821; P = 0.007), and fibrosis (OR = 0.590; 95% CI, 0.361−0.965; P = 0.035). In patients carrying A-INS, HSD17B13 levels decreased proportionally to allele dosage. Whole-transcriptome genotype profiling showed overrepresented immune response-related pathways. Thus, the rs72613567 A-INS allele reduces the risk of NASH and progressive liver damage and may become a therapeutic target.
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Garaycoechea, Martin. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina
Fil: Arrese, Marco. Pontificia Universidad Católica de Chile; Chile
Fil: San Martino, Julio. Hospital Diego Thompson; Argentina
Fil: Gazzi, Carla. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Casta&ntildeo, Gustavo O. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
description Hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567 genotypes and the hepatic transcriptome. The A-INS allele protected against NAFLD [odds ratio (OR) per adenine allele = 0.667; 95% CI, 0.486−0.916; P = 0.012]; this effect was nonsignificant when logistic regression analysis included BMI. The A-INS allele protected against nonalcoholic steatohepatitis (NASH) (OR = 0.612; 95% CI, 0.388−0.964; P = 0.033), ballooning degeneration (OR = 0.474; 95% CI, 0.267−0.842; P = 0.01), lobular inflammation (OR = 0.475; 95% CI, 0.275−0.821; P = 0.007), and fibrosis (OR = 0.590; 95% CI, 0.361−0.965; P = 0.035). In patients carrying A-INS, HSD17B13 levels decreased proportionally to allele dosage. Whole-transcriptome genotype profiling showed overrepresented immune response-related pathways. Thus, the rs72613567 A-INS allele reduces the risk of NASH and progressive liver damage and may become a therapeutic target.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
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/11336/94156
Pirola, Carlos José; Garaycoechea, Martin; Flichman, Diego Martin; Arrese, Marco; San Martino, Julio; et al.; Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 60; 1; 10-2018; 176-185
0022-2275
1539-7262
CONICET Digital
CONICET
url http://hdl.handle.net/11336/94156
identifier_str_mv Pirola, Carlos José; Garaycoechea, Martin; Flichman, Diego Martin; Arrese, Marco; San Martino, Julio; et al.; Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 60; 1; 10-2018; 176-185
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/url/http://www.jlr.org/lookup/doi/10.1194/jlr.P089953
info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.P089953
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 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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score 13.13397

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