Universität zu Köln

Krawczyk, Marcin ORCID: 0000-0002-0113-0777, Rau, Monika ORCID: 0000-0003-1219-4044, Schattenberg, Jorn M. ORCID: 0000-0002-4224-4703, Bantel, Heike, Pathil, Anita, Demir, Munevver, Kluwe, Johannes, Boettler, Tobias ORCID: 0000-0002-1195-055X, Lammert, Frank and Geier, Andreas (2017). Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study. J. Lipid Res., 58 (1). S. 247 - 256. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1539-7262

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Abstract

The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants represent genetic risk factors for nonalcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in patients with NAFLD. We recruited 515 patients with NAFLD (age 16-88 years, 280 female patients). Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7 variants. Carriers of the PNPLA3 and TM6SF2 risk alleles showed increased serum aspartate aminotransferase and alanine transaminase activities (P < 0.05). The PNPLA3 genotype was associated with steatosis grades S2-S3 (P < 0.001) and fibrosis stages F2-F4 (P < 0.001). The TM6SF2 genotype was associated with steatosis (P = 0.003) but not with fibrosis (P > 0.05). The MBOAT7 variant was solely associated with increased fibrosis (P = 0.046). In the multivariate model, variants PNPLA3 (P = 0.004) and TM6SF2 (P = 0.038) were associated with steatosis. Fibrosis stages were affected by the PNPLA3 (P = 0.042) and MBOAT7 (P = 0.021) but not by the TM6SF2 polymorphism (P > 0.05).(Jlr) The PNPLA3, TM6SF2, and MBOAT7 variants are associated with increased liver injury. The TM6SF2 variant seems to modulate predominantly hepatic fat accumulation, whereas the MBOAT7 polymorphism is linked to fibrosis. The PNPLA3 polymorphism confers risk of both increased steatosis and fibrosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Krawczyk, Marcin UNSPECIFIED orcid.org/0000-0002-0113-0777 UNSPECIFIED Rau, Monika UNSPECIFIED orcid.org/0000-0003-1219-4044 UNSPECIFIED Schattenberg, Jorn M. UNSPECIFIED orcid.org/0000-0002-4224-4703 UNSPECIFIED Bantel, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Pathil, Anita UNSPECIFIED UNSPECIFIED UNSPECIFIED Demir, Munevver UNSPECIFIED UNSPECIFIED UNSPECIFIED Kluwe, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Boettler, Tobias UNSPECIFIED orcid.org/0000-0002-1195-055X UNSPECIFIED Lammert, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Geier, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-243625
DOI:	10.1194/jlr.P067454
Journal or Publication Title:	J. Lipid Res.
Volume:	58
Number:	1
Page Range:	S. 247 - 256
Date:	2017
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1539-7262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NONALCOHOLIC FATTY LIVER; SUPERFAMILY MEMBER 2; CHRONIC HEPATITIS-C; E167K VARIANT; CONFERS SUSCEPTIBILITY; GENETIC-VARIATION; WIDE ASSOCIATION; INCREASES RISK; DISEASE; FIBROSIS Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24362