These authors contributed equally to this work.
Article first published online: 14 OCT 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 5, pages 1883–1891, November 2012
How to Cite
Grünhage, F., Hochrath, K., Krawczyk, M., Höblinger, A., Obermayer-Pietsch, B., Geisel, J., Trauner, M., Sauerbruch, T. and Lammert, F. (2012), Common genetic variation in vitamin D metabolism is associated with liver stiffness. Hepatology, 56: 1883–1891. doi: 10.1002/hep.25830
Potential conflict of interest: Dr. Höblinger received grants from Roche and Novartis.
Supported by BONFOR (Bonner Forschungsförderprogramm) and HOMFOR Saarland University research program. This work was also financed by the Deutsche Forschungsgemeinschaft (DFG Collaboration Research Centre SFB/TRR 57 TP 01, LA 997/5-1 and LA997/6-1 to F.L.). 25(OH)-vitamin D measurements were supported by BioPersMed (COMET K-project 825329), which is funded by the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT) and the Austrian Federal Ministry of Economics and Labour/the Federal Ministry of Economy, Family and Youth (BMWA/BMWFJ) and the Styrian Business Promotion Agency (SFG).
- Issue published online: 31 OCT 2012
- Article first published online: 14 OCT 2012
- Accepted manuscript online: 10 MAY 2012 06:45AM EST
- Manuscript Accepted: 2 MAY 2012
- Manuscript Received: 5 JUL 2011
Recently, genome-wide studies identified genetic variants that affect serum 25-hydroxyvitamin D levels in healthy populations (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, at CYP2R1; and rs7041, at vitamin D binding protein, GC). Because vitamin D deficiency is associated with advanced liver disease, we hypothesized that these variants are associated with 25(OH)-vitamin D levels and liver fibrosis. Overall, 712 Caucasian patients with chronic liver diseases were included. Liver fibrosis was assessed by transient elastography (TE) and/or histology. Serum levels of 25(OH)-vitamin D were correlated with TE and fibrosis stages. Genotypes were determined using TaqMan assays and tested for association with vitamin D and liver stiffness. Serum 25(OH)-vitamin D levels were inversely correlated with liver stiffness and histology (P < 0.001). Homozygous carriers of the rare DHCR7 allele or the common CYP2R1 allele presented with reduced 25(OH)-vitamin D levels (P < 0.05). The variant rs12785878 in the DHCR7 locus was associated with liver stiffness in both patients with TE <7.0 kPa and TE between 7.0 and 9.5 kPa. 25(OH)-vitamin D levels correlated with sunshine hours at the time of inclusion (P < 0.001). Conclusion: Common variation in 25(OH)-vitamin D metabolism is associated with liver stiffness in patients presenting with low to moderately increased elasticity. Although the susceptible DHCR7 genotype confers small risk, we speculate that the observed stiffness differences indicate a stronger influence of 25(OH)-vitamin D on initiation rather than progression of hepatic fibrosis. (HEPATOLOGY 2012;56:1883–1891)