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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-54501

Baur, K; Mertens, J C; Schmitt, J; Iwata, R; Stieger, B; Eloranta, J J; Frei, P; Stickel, F; Dill, M T; Seifert, Burkhardt; Bischoff Ferrari, H A; von Eckardstein, A; Bochud, P Y; Müllhaupt, B; Geier, A (2012). Combined effect of 25-OH vitamin D plasma levels and genetic Vitamin D Receptor (NR 1I1) variants on fibrosis progression rate in HCV patients. Liver International, 32(4):635-643.

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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. AIMS: 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). CONCLUSION: 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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
04 Faculty of Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > Center on Aging and Mobility
DDC:360 Social problems & social services
610 Medicine & health
300 Social sciences, sociology & anthropology
540 Chemistry
Language:English
Date:2012
Deposited On:16 Jan 2012 21:13
Last Modified:20 Dec 2013 19:00
Publisher:Wiley-Blackwell
ISSN:1478-3223
Publisher DOI:10.1111/j.1478-3231.2011.02674.x
PubMed ID:22151003
Citations:Web of Science®. Times Cited: 15
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