In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-07-03)
Kurzfassung:
Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C 〉 T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08–2.55; n = 765), particularly in those without advanced fibrosis (p 〈 0.001). The risk T allele was linked to 3’-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3 , TM6SF2 , and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p 〈 0.001), but did not significantly improve their predictive accuracy. When combining data from an independent UK NAFLD cohort, in the overall cohort of non-cirrhotic patients (n = 913, 41 with HCC) the T allele remained associated with HCC (OR 2.10, 1.33–3.31). Finally, in a combined cohort of non-cirrhotic patients with chronic hepatitis C or alcoholic liver disease (n = 1121), the T allele was independently associated with HCC risk (OR 1.93, 1.07–3.58). In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.
Materialart:
Online-Ressource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-04991-0
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2017
ZDB Id:
2615211-3
