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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/86714
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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 Técnicas2025-09-03T10:05:36Zoai: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:34982025-09-03 10:05:37.244CONICET 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/ |
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openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Nature |
publisher.none.fl_str_mv |
Nature |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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