The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients.
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.
Division of Gastroenterology & Hepatology, University Hospital Zurich, Zurich, Switzerland.
Katharina
K
Baur
Joachim C
JC
Mertens
Johannes
J
Schmitt
Rika
R
Iwata
Bruno
B
Stieger
Pascal
P
Frei
Burkhardt
B
Seifert
Heike A
HA
Bischoff Ferrari
Arnold
A
von Eckardstein
Beat
B
Müllhaupt
Andreas
A
Geier
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood
D000998:Antiviral Agents; D018167:Receptors, Calcitriol; D014807:Vitamin D; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons