Combined effect of 25-OH vitamin D plasma levels and genetic Vitamin D Receptor (NR 1I1) variants on fibrosis progression rate in HCV patients

• Published in: Liver international 2012-04, Vol.32 (4), p.635-643
• Main Authors: Baur, Katharina, Mertens, Joachim C., Schmitt, Johannes, Iwata, Rika, Stieger, Bruno, Eloranta, Jyrki J., Frei, Pascal, Stickel, Felix, Dill, Michael T., Seifert, Burkhardt, Bischoff Ferrari, Heike A., von Eckardstein, Arnold, Bochud, Pierre-Yves, Müllhaupt, Beat, Geier, Andreas
• Format: Article
• Language: English
• Subjects: Calcitriol - blood; Cirrhosis; Disease Progression; Fibrosis; fibrosis progression; Gene polymorphism; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; Genotyping; Haplotypes; Haplotypes - genetics; hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - complications; Humans; Liver Cirrhosis - blood; Liver Cirrhosis - etiology; Liver Cirrhosis - physiopathology; Liver diseases; Multivariate Analysis; Plasma levels; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; Risk factors; Switzerland; VDR bAt-haplotype; vitamin D; vitamin D receptor polymorphisms; Vitamin D receptors
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2011.02674.x

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