Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease

Autores
Sookoian, Silvia Cristina; Flichman, Diego Martin; Castaño, Gustavo Osvaldo; Pirola, Carlos José
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Previous epidemiological studies suggest that patients diagnosed with nonalcoholic fatty liver disease (NAFLD) who drink light to moderate amounts of alcohol (up to ~30 g per day) have less severe histological lesions compared with nondrinkers. However, while the cross‐sectional nature of current evidence precludes assessment of causality, cumulative lifetime‐exposure of moderate alcohol consumption on histological outcomes has never been evaluated. Aim: To overcome these limitations, a Mendelian randomisation study was performed using a validated genetic variant (rs1229984 A;G) in the alcohol dehydrogenase (ADH1B) gene as a proxy of long‐term alcohol exposure. Methods: We first assessed whether the instrumental variant (rs1229984) was associated with the amount of alcohol consumption in our cohort. We further explored the association between the variant and histological outcomes; a sample of 466 individuals, including 266 patients with NAFLD confirmed by liver biopsy, was studied. Results: We found that carriers of the A‐allele consumed significantly lower amounts of alcohol compared with noncarriers (2.3 ± 5.3 vs. 8.18 ± 21 g per day, mean ± s.d., P = 0.03). The analysis of association with the disease severity showed that carriers of the A‐allele had lower degree of histological steatosis (1.76 ± 0.83 vs. 2.19 ± 0.78, P = 0.03) and lower scores of lobular inflammation (0.54 ± 0.65 vs. 0.95 ± 0.92, P = 0.02) and NAFLD‐Activity Score (2.9 ± 1.4 vs. 3.7 ± 1.4, P = 0.015) compared with noncarriers. Conclusion: Mendelian randomisation analysis suggests no beneficial effect of moderate alcohol consumption on NAFLD disease severity.
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
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
Higado Graso
Enfermedad Hepática Grasa No Alcohólica
Alcohol
Polimorfismo
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:11336/47274
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47274
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network_name_str CONICET Digital (CONICET)
spelling Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver diseaseSookoian, Silvia CristinaFlichman, Diego MartinCastaño, Gustavo OsvaldoPirola, Carlos JoséHigado GrasoEnfermedad Hepática Grasa No AlcohólicaAlcoholPolimorfismohttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: Previous epidemiological studies suggest that patients diagnosed with nonalcoholic fatty liver disease (NAFLD) who drink light to moderate amounts of alcohol (up to ~30 g per day) have less severe histological lesions compared with nondrinkers. However, while the cross‐sectional nature of current evidence precludes assessment of causality, cumulative lifetime‐exposure of moderate alcohol consumption on histological outcomes has never been evaluated. Aim: To overcome these limitations, a Mendelian randomisation study was performed using a validated genetic variant (rs1229984 A;G) in the alcohol dehydrogenase (ADH1B) gene as a proxy of long‐term alcohol exposure. Methods: We first assessed whether the instrumental variant (rs1229984) was associated with the amount of alcohol consumption in our cohort. We further explored the association between the variant and histological outcomes; a sample of 466 individuals, including 266 patients with NAFLD confirmed by liver biopsy, was studied. Results: We found that carriers of the A‐allele consumed significantly lower amounts of alcohol compared with noncarriers (2.3 ± 5.3 vs. 8.18 ± 21 g per day, mean ± s.d., P = 0.03). The analysis of association with the disease severity showed that carriers of the A‐allele had lower degree of histological steatosis (1.76 ± 0.83 vs. 2.19 ± 0.78, P = 0.03) and lower scores of lobular inflammation (0.54 ± 0.65 vs. 0.95 ± 0.92, P = 0.02) and NAFLD‐Activity Score (2.9 ± 1.4 vs. 3.7 ± 1.4, P = 0.015) compared with noncarriers. Conclusion: Mendelian randomisation analysis suggests no beneficial effect of moderate alcohol consumption on NAFLD disease severity.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; 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; ArgentinaWiley Blackwell Publishing, Inc2016-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47274Sookoian, Silvia Cristina; Flichman, Diego Martin; Castaño, Gustavo Osvaldo; Pirola, Carlos José; Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease; Wiley Blackwell Publishing, Inc; Alimentary Pharmacology & Therapeutics.; 44; 11-12; 12-2016; 1224-12340269-2813CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/apt.13828info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/apt.13828info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:12:43Zoai:ri.conicet.gov.ar:11336/47274instacron: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:34982025-10-22 11:12:43.89CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
title Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
spellingShingle Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
Sookoian, Silvia Cristina
Higado Graso
Enfermedad Hepática Grasa No Alcohólica
Alcohol
Polimorfismo
title_short Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
title_full Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
title_fullStr Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
title_full_unstemmed Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
title_sort Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease
dc.creator.none.fl_str_mv Sookoian, Silvia Cristina
Flichman, Diego Martin
Castaño, Gustavo Osvaldo
Pirola, Carlos José
author Sookoian, Silvia Cristina
author_facet Sookoian, Silvia Cristina
Flichman, Diego Martin
Castaño, Gustavo Osvaldo
Pirola, Carlos José
author_role author
author2 Flichman, Diego Martin
Castaño, Gustavo Osvaldo
Pirola, Carlos José
author2_role author
author
author
dc.subject.none.fl_str_mv Higado Graso
Enfermedad Hepática Grasa No Alcohólica
Alcohol
Polimorfismo
topic Higado Graso
Enfermedad Hepática Grasa No Alcohólica
Alcohol
Polimorfismo
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: Previous epidemiological studies suggest that patients diagnosed with nonalcoholic fatty liver disease (NAFLD) who drink light to moderate amounts of alcohol (up to ~30 g per day) have less severe histological lesions compared with nondrinkers. However, while the cross‐sectional nature of current evidence precludes assessment of causality, cumulative lifetime‐exposure of moderate alcohol consumption on histological outcomes has never been evaluated. Aim: To overcome these limitations, a Mendelian randomisation study was performed using a validated genetic variant (rs1229984 A;G) in the alcohol dehydrogenase (ADH1B) gene as a proxy of long‐term alcohol exposure. Methods: We first assessed whether the instrumental variant (rs1229984) was associated with the amount of alcohol consumption in our cohort. We further explored the association between the variant and histological outcomes; a sample of 466 individuals, including 266 patients with NAFLD confirmed by liver biopsy, was studied. Results: We found that carriers of the A‐allele consumed significantly lower amounts of alcohol compared with noncarriers (2.3 ± 5.3 vs. 8.18 ± 21 g per day, mean ± s.d., P = 0.03). The analysis of association with the disease severity showed that carriers of the A‐allele had lower degree of histological steatosis (1.76 ± 0.83 vs. 2.19 ± 0.78, P = 0.03) and lower scores of lobular inflammation (0.54 ± 0.65 vs. 0.95 ± 0.92, P = 0.02) and NAFLD‐Activity Score (2.9 ± 1.4 vs. 3.7 ± 1.4, P = 0.015) compared with noncarriers. Conclusion: Mendelian randomisation analysis suggests no beneficial effect of moderate alcohol consumption on NAFLD disease severity.
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
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 Background: Previous epidemiological studies suggest that patients diagnosed with nonalcoholic fatty liver disease (NAFLD) who drink light to moderate amounts of alcohol (up to ~30 g per day) have less severe histological lesions compared with nondrinkers. However, while the cross‐sectional nature of current evidence precludes assessment of causality, cumulative lifetime‐exposure of moderate alcohol consumption on histological outcomes has never been evaluated. Aim: To overcome these limitations, a Mendelian randomisation study was performed using a validated genetic variant (rs1229984 A;G) in the alcohol dehydrogenase (ADH1B) gene as a proxy of long‐term alcohol exposure. Methods: We first assessed whether the instrumental variant (rs1229984) was associated with the amount of alcohol consumption in our cohort. We further explored the association between the variant and histological outcomes; a sample of 466 individuals, including 266 patients with NAFLD confirmed by liver biopsy, was studied. Results: We found that carriers of the A‐allele consumed significantly lower amounts of alcohol compared with noncarriers (2.3 ± 5.3 vs. 8.18 ± 21 g per day, mean ± s.d., P = 0.03). The analysis of association with the disease severity showed that carriers of the A‐allele had lower degree of histological steatosis (1.76 ± 0.83 vs. 2.19 ± 0.78, P = 0.03) and lower scores of lobular inflammation (0.54 ± 0.65 vs. 0.95 ± 0.92, P = 0.02) and NAFLD‐Activity Score (2.9 ± 1.4 vs. 3.7 ± 1.4, P = 0.015) compared with noncarriers. Conclusion: Mendelian randomisation analysis suggests no beneficial effect of moderate alcohol consumption on NAFLD disease severity.
publishDate 2016
dc.date.none.fl_str_mv 2016-12
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/11336/47274
Sookoian, Silvia Cristina; Flichman, Diego Martin; Castaño, Gustavo Osvaldo; Pirola, Carlos José; Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease; Wiley Blackwell Publishing, Inc; Alimentary Pharmacology & Therapeutics.; 44; 11-12; 12-2016; 1224-1234
0269-2813
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47274
identifier_str_mv Sookoian, Silvia Cristina; Flichman, Diego Martin; Castaño, Gustavo Osvaldo; Pirola, Carlos José; Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease; Wiley Blackwell Publishing, Inc; Alimentary Pharmacology & Therapeutics.; 44; 11-12; 12-2016; 1224-1234
0269-2813
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/apt.13828
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/apt.13828
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
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, 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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