Oral Presentations
Session Title: Parallel Session: PORTAL HYPERTENSION
Presentation Date: 02 APR, 2011
ASSOCIATION OF GENES REGULATING VITAMIN D HOMOEOSTASIS WITH VITAMIN D LEVELS AND LIVER FIBROSIS IN A COHORT OF PATIENTS WITH CHRONIC LIVER DISEASE
F. Grünhage1*, K. Hochrath1, M. Krawczyk1, B. Obermayer-Pietsch2, M. Trauner3, F. Lammert1
1Department of Medicine II, Saarland University Hospital, Homburg, Germany, 2Department of Internal Medicine, Medical University of Graz, Graz, 3Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. *frank.***@****
Background: Recently, genome wide studies identified a number of genetic variants that affect on vitamin D levels in healthy populations (rs12785878, near DHCR7; rs10741657, near CYP2R1 and rs7041 vitamin D binding protein GC; Wang et al. Lancet 2010). Since vitamin D deficiency is associated with advanced liver disease, we hypothesized that these variants are associated with vitamin D levels and fibrosis in patients with chronic liver disease.
Patients and methods: Overall, 834 patients with chronic liver disease and predominantly Caucasian descent (n=712; 85%) were included. Levels of 25(OH)-vitamin D3 were determined and liver stiffness was measured using transient elastography (TE). Patients were stratified in different fibrosis stages according to TE results (F0-F1 12.0 kPa). Genotypes were determined using Taqman assays.
Results: Most patients suffered from chronic viral hepatitis C (58.9%), followed by alcoholic (10.6%) and autoimmune (AIH, PBC, PSC) liver diseases (8.1%). Mean 25(OH)-vitamin D3 levels were 28.4 ± 15.8 ng/ml. Patients with advanced fibrosis (> 12.0 kPa) had significantly lower 25(OH)-vitamin D3 levels as compared to patients with < 12.0 kPa (21.7 vs. 29.7 ng/ml; p< 0.001). 25(OH)-vitamin D3 levels were inversely correlated with liver stiffness (p 7.0 kPa), the rare allele was significantly associated with increased liver stiffness (TT & TG vs GG: 5.1 ± 1.0 kPa vs. 5.4 ± 1.0 kPa; p < 0.05).
Conclusion: A common SNP close the DHCR7 gene is associated with 25(OH)-vitamin D3 serum concentrations in patients with chronic liver disease. Interestingly, the association of this SNP with liver fibrosis was restricted to patients with no or mild fibrosis, suggesting that the modifier effect of vitamin D might only be discernible during fibrosis initiation and early fibrosis stages.