Please use this identifier to cite or link to this item: doi:10.22028/D291-27432
Title: Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway
Author(s): Krawczyk, Marcin
Grünhage, Frank
Lammert, Frank
Language: English
Title: International Journal of Molecular Sciences
Volume: 14
Issue: 10
Startpage: 21153
Endpage: 21166
Publisher/Platform: MDPI
Year of Publication: 2013
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with liver stiffness. In 899 individuals (aged 17–83 years, 547 males) with chronic liver diseases, hepatic fibrosis was non-invasively phenotyped by transient elastography (TE). The SREBP1c single nucleotide polymorphisms (SNPs) were genotyped using PCR-based assays with 5'-nuclease and fluorescence detection. The SREBP1c rs11868035 variant affected liver fibrosis significantly (p = 0.029): median TE levels were 7.2, 6.6 and 6.0 kPa in carriers of (TT) (n = 421), (CT) (n = 384) and (CC) (n = 87) genotypes, respectively. Overall, the SREBP1c SNP was associated with low TE levels (5.0–8.0 kPa). Carriers of both PNPLA3 and SREBP1c risk genotypes displayed significantly (p = 0.005) higher median liver stiffness, as compared to patients carrying none of these variants. The common SREBP1c variant may affect early stages of liver fibrosis. Our study supports a role of the SREBP1c-PNPLA3 pathway as a “disease module” that promotes hepatic fibrogenesis.
DOI of the first publication: 10.3390/ijms141021153
Link to this record: urn:nbn:de:bsz:291--ds-274324
ISSN: 1422-0067
Date of registration: 3-Jan-2020
Faculty: M - Medizinische Fakultät
Department: M - Innere Medizin
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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