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The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients.
- Source :
-
Antiviral therapy [Antivir Ther] 2012; Vol. 17 (3), pp. 541-7. Date of Electronic Publication: 2011 Dec 14. - Publication Year :
- 2012
-
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.<br />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).<br />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).<br />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.
- Subjects :
- Adult
Aged
Cohort Studies
Drug Therapy, Combination
Female
Genotype
Hepacivirus genetics
Hepatitis C, Chronic virology
Humans
Interferons therapeutic use
Male
Middle Aged
Polyethylene Glycols therapeutic use
Ribavirin therapeutic use
Treatment Outcome
Vitamin D blood
Antiviral Agents therapeutic use
Haplotypes genetics
Hepacivirus drug effects
Hepatitis C, Chronic drug therapy
Hepatitis C, Chronic genetics
Polymorphism, Genetic
Receptors, Calcitriol genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2040-2058
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Antiviral therapy
- Publication Type :
- Academic Journal
- Accession number :
- 22300961
- Full Text :
- https://doi.org/10.3851/IMP2018