title: Combined effect of 25-OH vitamin D plasma levels and genetic vitamin D receptor (NR 1I1) variants on fibrosis progression rate in HCV patients.
abstract: BACKGROUND
  Decreased vitamin D levels have been described in various forms of chronic liver disease and associated with advanced fibrosis. Whether this association is a cause or consequence of advanced fibrosis remains unclear to date.
  
  
  OBJECTIVE
  To analyse combined effects of 25-OH vitamin D plasma levels and vitamin D receptor gene (VDR; NR1I1) polymorphisms on fibrosis progression rate in HCV patients.
  
  
  METHODS
  251 HCV patients underwent VDR genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 A and TaqI rs731236 A). Plasma 25-OH vitamin D levels were quantified in a subgroup of 97 patients without advanced fibrosis. The VDR haplotype and genotypes as well as plasma 25-OH vitamin D levels were associated with fibrosis progression.
  
  
  RESULTS
  The bAt[CCA]-haplotype was significantly associated with fibrosis progression >0.101 U/year (P = 0.007; OR = 2.02) and with cirrhosis (P = 0.022; OR = 1.84). Forty-five percent of bAt[CCA]-haplotype patients were rapid fibrosers, 21.1% were cirrhotic. Likewise, ApaI rs7975232 CC genotype was significantly associated with fibrosis progression and cirrhosis. Lower plasma 25-OH vitamin D levels were significantly associated with fibrosis progression >0.101 U/year in F0-2 patients (P = 0.013). Combined analysis of both variables revealed a highly significant additive effect on fibrosis progression with 45.5% rapid fibrosers for bAt[CCA]-haplotype and 25-OH vitamin D < 20 μg/L compared with only 9.1% for the most favourable combination (P = 0.006). In multivariate analysis, the bAt-haplotype was an independent risk factor for fibrosis progression (P = 0.001; OR = 2.83).
  
  
  CONCLUSIONS
  Low 25-OH vitamin D plasma levels and the unfavourable VDR bAt[CCA]-haplotype are associated with rapid fibrosis progression in chronic HCV patients. In combination, both variables exert significant additive effects on fibrosis progression.
authors.affiliation: Division of Gastroenterology & Hepatology, University Hospital Zurich (USZ), Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Baur
authors.forename: Joachim C
authors.initials: JC
authors.lastname: Mertens
authors.forename: Johannes
authors.initials: J
authors.lastname: Schmitt
authors.forename: Rika
authors.initials: R
authors.lastname: Iwata
authors.forename: Bruno
authors.initials: B
authors.lastname: Stieger
authors.forename: Jyrki J
authors.initials: JJ
authors.lastname: Eloranta
authors.forename: Pascal
authors.initials: P
authors.lastname: Frei
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Michael T
authors.initials: MT
authors.lastname: Dill
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Heike A Bischoff
authors.initials: HA
authors.lastname: Ferrari
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
mesh_terms: D002117:Calcitriol / Q000097:blood*; D018450:Disease Progression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D015999:Multivariate Analysis; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D013557:Switzerland
chemical_list: D018167:Receptors, Calcitriol; D002117:Calcitriol