Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway
Department of Medicine II, Saarland University Medical Center, Homburg 66421, Germany
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Author to whom correspondence should be addressed.
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These authors contributed equally to this work.
Int. J. Mol. Sci. 2013, 14(10), 21153-21166; https://doi.org/10.3390/ijms141021153
Received: 27 August 2013 / Revised: 15 October 2013 / Accepted: 16 October 2013 / Published: 22 October 2013
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
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.
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MDPI and ACS Style
Krawczyk, M.; Grünhage, F.; Lammert, F. Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway. Int. J. Mol. Sci. 2013, 14, 21153-21166. https://doi.org/10.3390/ijms141021153
AMA Style
Krawczyk M, Grünhage F, Lammert F. Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway. International Journal of Molecular Sciences. 2013; 14(10):21153-21166. https://doi.org/10.3390/ijms141021153
Chicago/Turabian StyleKrawczyk, Marcin; Grünhage, Frank; Lammert, Frank. 2013. "Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway" Int. J. Mol. Sci. 14, no. 10: 21153-21166. https://doi.org/10.3390/ijms141021153
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