Z Gastroenterol 2011; 49 - V1_02
DOI: 10.1055/s-0030-1269516

Association of common SNPs of genes regulating vitamin D homoeostasis with vitamin D levels and liver fibrosis in a cohort of patients with chronic liver disease

F Grünhage 1, K Hochrath 2, M Krawczyk 1, B Obermayer-Pietsch 3, M Trauner 4, F Lammert 1
  • 1Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany, Homburg
  • 2Abteilung für Innere Medizin II, Saarland, Homburg
  • 3Department of Internal Medicine, Graz, Austria
  • 4Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

Aims: Recently, genome wide studies identified genetic variants that affect 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 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 <7.0 kPa; F2: 7.0–9.0 kPa; F3: 9.0–12.0 kPa; F4 >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 vitamin D3 levels as compared to patients with <12.0 kPa (21.7 vs. 29.7 ng/ml; p<0.001). Vitamin D3 levels were inveresely correlated with liver stiffness (p<0.001). We detected an association with fibrosis for rs12785878. Interestingly, this SNP was not associated with liver fibrosis in the overall cohort. However after exclusion of patients with advanced fibrosis (>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 vitamin D3 serum concentrations in patients with chronic liver disease. Interestingly, the association of this SNP with liver fibrosis was restricted no or mild fibrosis, suggesting that the modulatory role of vitamin D might only be discernible during fibrosis initiation and early fibrosis.