Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease

Autores
Sookoian, Silvia Cristina; Flichman, Diego Martin; Garaycoechea, Martin E.; Gazzi, Carla; San Martino, Julio; Castaño, Gustavo Osvaldo; Pirola, Carlos José
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Current knowledge on the genetic basis of nonalcoholic fatty liver disease (NAFLD) suggests that variants contributing not only to the disease predisposition but histological severity as well are located in genes that regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4 (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case-control study. Our sample included 634 individuals (372 patients with NAFLD diagnosed by liver biopsy and 262 control subjects); genotyping was performed by a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor allele frequency 40.8%. Our sample had 84-99% power if an additive genetic model is assumed for estimated odds ratios of 1.3-1.5, respectively. We found no evidence of association between rs641738 and either NAFLD (Cochran-Armitage test for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7 protein expression were found in the liver of patients with NAFLD, which were unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the pathogenesis of NAFLD is inconclusive.
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
Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garaycoechea, Martin E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Gazzi, Carla. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: San Martino, Julio. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martín; Argentina
Fil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
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
Materia
NASH
NAFLD
GENETICS
MBOAT7
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:11336/86714
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/86714
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver DiseaseSookoian, Silvia CristinaFlichman, Diego MartinGaraycoechea, Martin E.Gazzi, CarlaSan Martino, JulioCastaño, Gustavo OsvaldoPirola, Carlos JoséNASHNAFLDGENETICSMBOAT7https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Current knowledge on the genetic basis of nonalcoholic fatty liver disease (NAFLD) suggests that variants contributing not only to the disease predisposition but histological severity as well are located in genes that regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4 (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case-control study. Our sample included 634 individuals (372 patients with NAFLD diagnosed by liver biopsy and 262 control subjects); genotyping was performed by a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor allele frequency 40.8%. Our sample had 84-99% power if an additive genetic model is assumed for estimated odds ratios of 1.3-1.5, respectively. We found no evidence of association between rs641738 and either NAFLD (Cochran-Armitage test for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7 protein expression were found in the liver of patients with NAFLD, which were unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the pathogenesis of NAFLD is inconclusive.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; ArgentinaFil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garaycoechea, Martin E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Gazzi, Carla. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: San Martino, Julio. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martín; ArgentinaFil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: 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; ArgentinaNature2018-12info: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/11336/86714Sookoian, Silvia Cristina; Flichman, Diego Martin; Garaycoechea, Martin E.; Gazzi, Carla; San Martino, Julio; et al.; Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease; Nature; Scientific Reports; 8; 1; 12-2018; 5097-51082045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-018-23453-9info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-23453-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:27:12Zoai:ri.conicet.gov.ar:11336/86714instacron: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 10:27:12.756CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
title Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
spellingShingle Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
Sookoian, Silvia Cristina
NASH
NAFLD
GENETICS
MBOAT7
title_short Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
title_full Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
title_fullStr Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
title_full_unstemmed Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
title_sort Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease
dc.creator.none.fl_str_mv Sookoian, Silvia Cristina
Flichman, Diego Martin
Garaycoechea, Martin E.
Gazzi, Carla
San Martino, Julio
Castaño, Gustavo Osvaldo
Pirola, Carlos José
author Sookoian, Silvia Cristina
author_facet Sookoian, Silvia Cristina
Flichman, Diego Martin
Garaycoechea, Martin E.
Gazzi, Carla
San Martino, Julio
Castaño, Gustavo Osvaldo
Pirola, Carlos José
author_role author
author2 Flichman, Diego Martin
Garaycoechea, Martin E.
Gazzi, Carla
San Martino, Julio
Castaño, Gustavo Osvaldo
Pirola, Carlos José
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv NASH
NAFLD
GENETICS
MBOAT7
topic NASH
NAFLD
GENETICS
MBOAT7
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Current knowledge on the genetic basis of nonalcoholic fatty liver disease (NAFLD) suggests that variants contributing not only to the disease predisposition but histological severity as well are located in genes that regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4 (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case-control study. Our sample included 634 individuals (372 patients with NAFLD diagnosed by liver biopsy and 262 control subjects); genotyping was performed by a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor allele frequency 40.8%. Our sample had 84-99% power if an additive genetic model is assumed for estimated odds ratios of 1.3-1.5, respectively. We found no evidence of association between rs641738 and either NAFLD (Cochran-Armitage test for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7 protein expression were found in the liver of patients with NAFLD, which were unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the pathogenesis of NAFLD is inconclusive.
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
Fil: Flichman, Diego Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garaycoechea, Martin E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Gazzi, Carla. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: San Martino, Julio. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martín; Argentina
Fil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
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
description Current knowledge on the genetic basis of nonalcoholic fatty liver disease (NAFLD) suggests that variants contributing not only to the disease predisposition but histological severity as well are located in genes that regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4 (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case-control study. Our sample included 634 individuals (372 patients with NAFLD diagnosed by liver biopsy and 262 control subjects); genotyping was performed by a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor allele frequency 40.8%. Our sample had 84-99% power if an additive genetic model is assumed for estimated odds ratios of 1.3-1.5, respectively. We found no evidence of association between rs641738 and either NAFLD (Cochran-Armitage test for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7 protein expression were found in the liver of patients with NAFLD, which were unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the pathogenesis of NAFLD is inconclusive.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/86714
Sookoian, Silvia Cristina; Flichman, Diego Martin; Garaycoechea, Martin E.; Gazzi, Carla; San Martino, Julio; et al.; Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease; Nature; Scientific Reports; 8; 1; 12-2018; 5097-5108
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/86714
identifier_str_mv Sookoian, Silvia Cristina; Flichman, Diego Martin; Garaycoechea, Martin E.; Gazzi, Carla; San Martino, Julio; et al.; Lack of evidence supporting a role of TMC4-rs641738 missense variant - MBOAT7- intergenic downstream variant - In the Susceptibility to Nonalcoholic Fatty Liver Disease; Nature; Scientific Reports; 8; 1; 12-2018; 5097-5108
2045-2322
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.nature.com/articles/s41598-018-23453-9
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-23453-9
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 Nature
publisher.none.fl_str_mv Nature
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 13.070432

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