Show simple item record

dc.contributor.authorEslam, M
dc.contributor.authorMangia, A
dc.contributor.authorBerg, T
dc.contributor.authorChan, HLY
dc.contributor.authorIrving, WL
dc.contributor.authorDore, GJ
dc.contributor.authorAbate, ML
dc.contributor.authorBugianesi, E
dc.contributor.authorAdams, LA
dc.contributor.authorNajim, MAM
dc.contributor.authorMiele, L
dc.contributor.authorWeltman, M
dc.contributor.authorMollison, L
dc.contributor.authorCheng, W
dc.contributor.authorRiordan, S
dc.contributor.authorFischer, J
dc.contributor.authorRomero-Gomez, M
dc.contributor.authorSpengler, U
dc.contributor.authorNattermann, J
dc.contributor.authorRahme, A
dc.contributor.authorSheridan, D
dc.contributor.authorBooth, DR
dc.contributor.authorMcLeod, D
dc.contributor.authorPowell, E
dc.contributor.authorLiddle, C
dc.contributor.authorDouglas, MW
dc.contributor.authorvan der Poorten, D
dc.contributor.authorGeorge, J
dc.date.accessioned2016-08-11T08:32:30Z
dc.date.issued2016-06-22
dc.identifier.issn0270-9139
dc.identifier.issn1527-3350
dc.identifier.urihttp://hdl.handle.net/10026.1/5267
dc.description.abstract

<jats:p>A genome‐wide exome association study has identified the transmembrane 6 superfamily member 2 (<jats:italic toggle="yes">TM6SF2</jats:italic>) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of <jats:italic toggle="yes">TM6SF2</jats:italic> and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (<jats:italic toggle="yes">P</jats:italic> = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic <jats:italic toggle="yes">TM6SF2</jats:italic> and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted ≥F2 fibrosis in CHC and NAFLD assessed cross‐sectionally (odds ratio = 1.39, 95% confidence interval 1.04‐1.87, and odds ratio = 1.62, 95% confidence interval 1.03‐2.52, respectively; <jats:italic toggle="yes">P</jats:italic> &lt; 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. <jats:italic toggle="yes">Conclusion:</jats:italic> The <jats:italic toggle="yes">TM6SF2</jats:italic> E167K substitution promotes steatosis and lipid abnormalities in part by altering <jats:italic toggle="yes">TM6SF2</jats:italic> and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (H<jats:sc>epatology</jats:sc> 2016;64:34–46)</jats:p>

dc.format.extent34-46
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoen
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.subjectAdult
dc.subjectCase-Control Studies
dc.subjectCohort Studies
dc.subjectFemale
dc.subjectFibrosis
dc.subjectGenetic Predisposition to Disease
dc.subjectHepatitis, Viral, Human
dc.subjectHumans
dc.subjectLipid Metabolism
dc.subjectLiver
dc.subjectMale
dc.subjectMembrane Proteins
dc.subjectMiddle Aged
dc.subjectNon-alcoholic Fatty Liver Disease
dc.subjectPolymorphism, Single Nucleotide
dc.subjectViral Load
dc.titleDiverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes
dc.typejournal-article
dc.typeArticle
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/26822232
plymouth.issue1
plymouth.volume64
plymouth.publication-statusPublished
plymouth.journalHepatology
dc.identifier.doi10.1002/hep.28475
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeUnited States
dcterms.dateAccepted2016-01-27
dc.rights.embargodate2017-6-22
dc.identifier.eissn1527-3350
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1002/hep.28475
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-06-22
rioxxterms.typeJournal Article/Review


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record


All items in PEARL are protected by copyright law.
Author manuscripts deposited to comply with open access mandates are made available in accordance with publisher policies. Please cite only the published version using the details provided on the item record or document. In the absence of an open licence (e.g. Creative Commons), permissions for further reuse of content should be sought from the publisher or author.
Theme by 
Atmire NV