RGD Reference Report - Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy. - Rat Genome Database

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Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy.

Authors: Lange, Christian Markus  Bojunga, Jörg  Ramos-Lopez, Elizabeth  von Wagner, Michael  Hassler, Angela  Vermehren, Johannes  Herrmann, Eva  Badenhoop, Klaus  Zeuzem, Stefan  Sarrazin, Christoph 
Citation: Lange CM, etal., J Hepatol. 2011 May;54(5):887-93. doi: 10.1016/j.jhep.2010.08.036. Epub 2011 Jan 20.
RGD ID: 25671413
Pubmed: PMID:21145801   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jhep.2010.08.036   (Journal Full-text)


BACKGROUND & AIMS: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Chronic Hepatitis C severityIAGP 25671413DNA:polymorphism:promoter: 1260C>A (rs10877012) (human)RGD 
Chronic Hepatitis C severityISOCYP27B1 (Homo sapiens)25671413; 25671413DNA:polymorphism:promoter: 1260C>A (rs10877012) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Decreased circulating vitamin D concentration severityIAGP 25671413DNA:polymorphism:promoter: 1260C>A (rs10877012) (human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cyp27b1  (cytochrome P450, family 27, subfamily b, polypeptide 1)

Genes (Mus musculus)
Cyp27b1  (cytochrome P450, family 27, subfamily b, polypeptide 1)

Genes (Homo sapiens)
CYP27B1  (cytochrome P450 family 27 subfamily B member 1)


Additional Information