title: MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response.
abstract: Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose-binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Zupin
authors.affiliation: Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Polesello
authors.affiliation: Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Alberi
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Moratelli
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: S L
authors.initials: SL
authors.lastname: Crocè
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Masutti
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pozzato
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.|Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Crovella
authors.affiliation: Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Segat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007167:Immunotherapy / Q000379:methods*; D016898:Interferon-alpha / Q000627:therapeutic use; D007558:Italy; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000235:genetics
chemical_list: D016898:Interferon-alpha; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a