title: Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy.
abstract: OBJECTIVE
  Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in hepatitis C virus (HCV) genotype 1 patients. We, therefore, performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms with functional relevance within the vitamin D cascade on chronic hepatitis C and its treatment.
  
  
  METHODS
  Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and 1α-hydroxylase were determined in a cohort of 468 HCV genotype 1, 2, and 3 infected patients who were treated with interferon-alfa based regimens.
  
  
  RESULTS
  Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D(3)<10 ng/ml in 25% versus 12%, p<0.00001). 25(OH)D(3) deficiency correlated with SVR in HCV genotype 2 and 3 patients (50% and 81% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.0001). In addition, the CYP27B1-1260 promoter polymorphism rs10877012 had substantial impact on 1,25-dihydroxyvitamin D serum levels (72, 61, and 60 pmol/ml for rs10877012 AA, AC, and CC, respectively, p=0.04) and on SVR rates in HCV genotype 1, 2, and 3 infected patients (77% and 65% versus 42% for rs10877012 AA, AC, and CC, respectively, p=0.02).
  
  
  CONCLUSIONS
  Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25-hydroxyvitamin D levels and CYP27B1-1260 promoter polymorphism leading to reduced 1,25-dihydroxyvitamin D levels are associated with failure to achieve SVR in HCV genotype 1, 2, and 3 infected patients.
authors.affiliation: Klinikum der J.W. Goethe-Universität Frankfurt am Main, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Christian Markus
authors.initials: CM
authors.lastname: Lange
authors.forename: Jörg
authors.initials: J
authors.lastname: Bojunga
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramos-Lopez
authors.forename: Michael
authors.initials: M
authors.lastname: von Wagner
authors.forename: Angela
authors.initials: A
authors.lastname: Hassler
authors.forename: Johannes
authors.initials: J
authors.lastname: Vermehren
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002112:Calcifediol / Q000097:blood; D024882:Drug Resistance, Viral / Q000276:immunology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D018167:Receptors, Calcitriol / Q000235:genetics; D012189:Retrospective Studies; D014808:Vitamin D Deficiency / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D018167:Receptors, Calcitriol; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol