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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-62299

Baur, Katharina; Mertens, Joachim C; Schmitt, Johannes; Iwata, Rika; Stieger, Bruno; Frei, Pascal; Seifert, Burkhardt; Ferrari, Heike A Bischoff; von Eckardstein, Arnold; Müllhaupt, Beat; Geier, Andreas (2012). The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients. Antiviral Therapy, 17(3):541-547.

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Abstract

BACKGROUND: Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients. METHODS: A total of 155 chronic hepatitis C patients were recruited from the Swiss Hepatitis C Cohort Study for NR1I1 genotyping and plasma 25-OH vitamin D level measurement. NR1I1 genotype data and combined effects of plasma 25-OH vitamin D level were analysed regarding therapy response (sustained virological response). RESULTS: A strong association was observed between therapy non-response and the NR1I1 CCA (bAt) haplotype consisting of rs1544410 (BsmI) C, rs7975232 (ApaI) C and rs731236 (TaqI) A alleles. Of the HCV patients carrying the CCA haplotype, 50.3% were non-responders (odds ratio [OR] 1.69, 95% CI 1.07, 2.67; P=0.028). A similar association was observed for the combinational CCCCAA genotype (OR 2.94, 95% CI 1.36, 6.37; P=0.007). The combinational CCCCAA genotype was confirmed as an independent risk factor for non-response in multivariate analysis (OR 2.50, 95% CI 1.07, 5.87; P=0.034). Analysing combined effects, a significant impact of low 25-OH vitamin D levels on sustained virological response were only seen in patients with the unfavourable NR1I1 CCA (bAt) haplotype (OR for non-SVR 3.55; 95% CI 1.005, 12.57; P=0.049). CONCLUSIONS: NR1I1 vitamin D receptor polymorphisms influence response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C and exert an additive genetic predisposition to previously described low 25-OH vitamin D serum levels.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
04 Faculty of Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
04 Faculty of Medicine > Center on Aging and Mobility
DDC:570 Life sciences; biology
360 Social problems & social services
610 Medicine & health
300 Social sciences, sociology & anthropology
540 Chemistry
Language:English
Date:2012
Deposited On:16 May 2012 15:16
Last Modified:27 Nov 2013 18:23
Publisher:International Medical Press
ISSN:1359-6535
Publisher DOI:10.3851/IMP2018
PubMed ID:22300961
Citations:Web of Science®. Times Cited: 7
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Scopus®. Citation Count: 8

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