title: Vitamin D pathway gene polymorphisms as predictors of hepatitis C virus-related mixed cryoglobulinemia.
abstract: Mixed cryoglobulinemia (MC) is the most frequent extrahepatic hepatitis C virus (HCV) complication. Vitamin D is a modulator of several biological processes, including immune and skeletal systems and MC presence and systemic vasculitis were associated independently with low levels of vitamin D. Considering the impact of vitamin D, we aimed to evaluate the role of some single nucleotide polymorphisms (SNPs) of vitamin D pathway genes in the prediction of MC in HCV patients treated with pegylated interferon and ribavirin. We investigated SNPs in IL-28B, CYP27B1, CYP27A1, CYP24A1, VDBP, and VDR genes through real-time PCR. VDR gene SNPs were related to baseline viral load: VDR BsmI AA (P=0.018), TaqI CC (P=0.009), and ApaI AA (P=0.004) showed a lower baseline HCV count. Among vitamin D pathway gene polymorphisms, VDR FokI T>C was a factor associated with the presence of MC in the study population (P=0.011): related to C allele carriers (TT vs. TC/CC), we obtained a P-value of 0.003. In the logistic regression analysis to assess which demographic, clinical, or genetic factors could predict the presence of cryoglobulin, the TT/CC IL-28B rs8099917/rs12979860 haplotype [P<0.001; odds ratio (OR) 3.516 (1.951-6.336)], baseline viral load [P<0.001; OR 1.000 (0.999-1.001)], and VDR FokI TC/CC genotypes [0.044; OR 0.463 (0.218-0.981)] remained in the final regression model. These data could help physicians identify patients with a higher probability of developing MC extrahepatic complications.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.forename: Lucio
authors.initials: L
authors.lastname: Boglione
authors.forename: Amedeo
authors.initials: A
authors.lastname: De Nicolò
authors.forename: Chiara Simona
authors.initials: CS
authors.lastname: Cardellino
authors.forename: Chiara
authors.initials: C
authors.lastname: Carcieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cariti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D003449:Cryoglobulinemia / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012189:Retrospective Studies; D015398:Signal Transduction; D019562:Viral Load; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D018167:Receptors, Calcitriol; D014807:Vitamin D