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Int. J. Mol. Sci. 2013, 14(10), 21153-21166; doi:10.3390/ijms141021153
Article

Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway

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Received: 27 August 2013; in revised form: 15 October 2013 / Accepted: 16 October 2013 / Published: 22 October 2013
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
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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.
Keywords: adiponutrin; gene variant; hepatic fibrosis; sterol regulatory binding protein 1c adiponutrin; gene variant; hepatic fibrosis; sterol regulatory binding protein 1c
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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.

Chicago/Turabian Style

Krawczyk, 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.


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