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dc.contributor.author
Sookoian, Silvia Cristina
dc.contributor.author
Castaño, Gustavo Osvaldo
dc.contributor.author
Scian, Romina
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Mallardi, Pablo
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Fernandez Gianotti, Tomas
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Burgueño, Adriana Laura
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San Martino, Julio
dc.contributor.author
Pirola, Carlos José
dc.date.available
2017-07-13T20:54:45Z
dc.date.issued
2015-02
dc.identifier.citation
Sookoian, Silvia Cristina; Castaño, Gustavo Osvaldo; Scian, Romina; Mallardi, Pablo; Fernandez Gianotti, Tomas; et al.; Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity; Wiley; Hepatology (baltimore, Md.); 61; 2; 2-2015; 515-526
dc.identifier.issn
0270-9139
dc.identifier.uri
http://hdl.handle.net/11336/20427
dc.description.abstract
We explored the role of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C/T nonsynonymous (p.Glu167Lys) variant in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and disease severity. A total of 361 individuals (135 control subjects and 226 patients with histologically proven NAFLD) were included in a sample with 97% power for the additive genetic model. A discrete trait analysis of NAFLD showed that rs58542926 was associated with a modest risk of fatty liver (P = 0.038; odds ratio [OR]: 1.37; 95% confidence interval [CI]: 1.02-1.84); nevertheless, conditioning on patatin-like phospholipase domain-containing 3 (PNPLA3)-rs738409 abolished this effect. We did not observe an interaction between rs738409 and rs58542926 variants on the risk of NAFLD. We observed a significant association of rs58542926 and disease severity (P = 0.027), but not lobular inflammation or fibrosis; rs58542926 was not associated with levels of liver enzymes. An allelic test showed that the T (Lys167) allele was significantly associated with disease progression (P = 0.021; OR, 1.66; 95% CI: 1.08-2.55). A significant association was found with the histological degree of liver steatosis (β, 0.15; standard error: 0.06; P = 0.0299) that was independent of rs738409. Homozygous carriers of the C (Glu167) allele showed increased risk for cardiovascular disease. TM6SF2 protein expression was decreased markedly in liver of NAFLD patients, compared to controls. In addition, TM6SF2 immunoreactivity was reduced in subjects carrying at least one copy of the T allele, consistent with a difference in liver allele-specific transcript abundance. Conclusion: rs58542926 is a low-frequency variant with a modest effect on NAFLD, suggesting that carriers of the T allele are slightly more likely to accumulate fat in the liver and develop nonalcoholic steatohepatitis than those without. TM6SF2 appears to play a significant role in disease biology.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Tm6sf2
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Gene Variants
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Fatty Liver
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Metabolism
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Gastroenterología y Hepatología
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-07-13T17:24:52Z
dc.journal.volume
61
dc.journal.number
2
dc.journal.pagination
515-526
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Hoboken
dc.description.fil
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
dc.description.fil
Fil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
dc.description.fil
Fil: Scian, Romina. 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
dc.description.fil
Fil: Mallardi, Pablo. Hospital Diego Thompson; Argentina
dc.description.fil
Fil: Fernandez Gianotti, Tomas. 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
dc.description.fil
Fil: Burgueño, Adriana Laura. 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
dc.description.fil
Fil: San Martino, Julio. Hospital Diego Thompson; Argentina
dc.description.fil
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
dc.journal.title
Hepatology (baltimore, Md.)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/hep.27556
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/hep.27556/abstract


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