Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597351
1. Fibrogenesis
Georg Thieme Verlag KG Stuttgart · New York

Presence of the MBOAT7 rs641738 variant might enhance liver fibrosis in patients with fatty liver: analysis of the German NAFLD CSG cohort

M Krawczyk
1   Saarland University Medical Center, Department of Medicine II, Homburg, Germany
,
M Rau
2   University Hospital Würzburg, Division of Hepatology, Department of Medicine II, Würzburg, Germany
,
JM Schattenberg
3   Johannes Gutenberg University, Department of Medicine I, University Medical Center Mainz, Mainz, Germany
,
H Bantel
4   Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
,
A Pathil
5   University of Heidelberg, Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg, Germany
,
M Demir
6   University Hospital of Cologne, Clinic for Gastroenterology and Hepatology, Cologne, Germany
,
J Kluwe
7   Hamburg University Medical Center, Department of Medicine I, Hamburg, Germany
,
T Boettler
8   University Hospital Freiburg, Department of Medicine II, Freiburg, Germany
,
F Lammert
1   Saarland University Medical Center, Department of Medicine II, Homburg, Germany
,
A Geier
2   University Hospital Würzburg, Division of Hepatology, Department of Medicine II, Würzburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2016 (online)

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Background and aims: Familial clustering of fatty liver underscores the role of genetic predisposition in the development of this condition. Recently the MBOAT7 rs641738 polymorphism has been detected as a novel prosteatotic variant (Mancina et al. Gastroenterology 2016) together with the established PNPLA3 p.I148 M and TM6SF2 p.E167K variants. In the current study we investigated the association of this variant with markers of liver injury in NAFLD patients.

Patients and methods: Overall, we recruited 515 patients with NAFLD (age 16 – 88 years, 280 females) in 8 German tertiary referral centers. Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the MBOAT7 rs641738 polymorphism. Serum concentrations of CK18-M30 fragment were measured by ELISA in 135 patients.

Results: The MBOAT7 genotype distribution was: [CC] n = 159, [CT] n = 242, and [TT] n = 114. Among 320 biopsied individuals 57% had steatosis grades 2 or 3. Fibrosis stage F2 or higher was present in 30% of patients, while liver cirrhosis was detected in 21 (6%) individuals. There was no difference in MBOAT7 genotype distribution in NAFLD patients with or without liver biopsy. On the other hand, the presence of this variant was associated with an increased risk of fibrosis (common OR = 1.44, P = 0.04), whilst not affecting serum ALT or ASL activities or CK18-M30 levels or liver steatosis (P > 0.05). In contrast to studies in patients with alcoholic liver disease (Buch S et al., Nat Genet 2015), we did not detect an association of this variant with liver cirrhosis in our cohort.

Conclusions: The MBOAT7 genotype might be associated with early stages of liver fibrosis in patients with NAFLD. Given the low number of individuals with advanced fibrosis in our cohort, genetic analyses of larger groups of patients with more prominent liver disease are necessary to delineate the association of the MBOAT7 variant with hepatic injury in the setting of NAFLD.