title: IFNL3 polymorphisms and HCV infection in patients with beta thalassemia.
abstract: BACKGROUND AND RATIONALE FOR THE STUDY: Genome-wide association studies have identified host genetic variation to be critical for spontaneous clearance and treatment response in patients infected with hepatitis C virus. Recently, the role of the IFNL3 polymorphisms in influencing the spontaneous clearance of HCV, the response to interferon and the progression of liver fibrosis, was also demonstrated in patients with thalassemia major infected by genotype 1b. In the present study we retrospectively analyzed 368 anti-HCV positive patients with beta-thalassemia at two Italian major centers in Cagliari and Torino.
  
  
  RESULTS
  C/C variant of polymorphism rs12979860 was related to response to interferon treatment and, above all, to spontaneous clearance of the virus. However, the positive predictive power was stronger for viral persistence than spontaneous clearance and in such respect the TT allele was more predictive than CC. The methylation associated polymorphism rs4803221 had independent effects with respect to rs12979860 and the haplotype tagged by SNP rs12979860 and rs4803221 significantly could improve the viral clearance prediction in infected patients. Neither necroinflammation or bilirubin values in the chronic phase of the hepatitis C were related to IFNL3 polymorphisms. No relation among IFNL3 polymorphisms and fibrosis stage directly shown by the liver biopsy was found.
  
  
  CONCLUSIONS
  Also in thalassemia the SNPs on chromosome 19q13 closely associates with spontaneous and treatment-induced HCV clearance. The viral clearance prediction is significantly improved by the haplotype tagged by SNP rs12979860 and rs4803221. Neither necroinflammation, bilirubin values or fibrosis stage seem to be related to IFNL3 polymorphisms.
authors: Clinica Pediatrica 2a, Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare-Università di Cagliari, Ospedale Regionale Microcitemie ASL8, Cagliari, Italy.
authors: Raffaella
authors: R
authors: Origa
authors: Clinica Pediatrica 2a, Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare-Università di Cagliari, Ospedale Regionale Microcitemie ASL8, Cagliari, Italy.
authors: Giuseppe
authors: G
authors: Marceddu
authors: Clinica Pediatrica 2a, Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare-Università di Cagliari, Ospedale Regionale Microcitemie ASL8, Cagliari, Italy.
authors: Fabrice
authors: F
authors: Danjou
authors: Istituto di Ricerca Genetica e Biomedica (IRGB) CNR, Cagliari, Italy.
authors: Luciana
authors: L
authors: Perseu
authors: Clinica Pediatrica 2a, Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare-Università di Cagliari, Ospedale Regionale Microcitemie ASL8, Cagliari, Italy.
authors: Stefania
authors: S
authors: Satta
authors: Clinica Pediatrica 2a, Dipartimento di Sanità Pubblica, Medicina Clinica e Molecolare-Università di Cagliari, Ospedale Regionale Microcitemie ASL8, Cagliari, Italy.
authors: Franca Rosa
authors: FR
authors: Demartis
authors: Thalassemia Center, University of Turin, Orbassano, Italy.
authors: Antonio
authors: A
authors: Piga
authors: Thalassemia Center, University of Turin, Orbassano, Italy.
authors: Filomena
authors: F
authors: Longo
authors: Ospedale Regionale per le Microcitemie, ASL8, Cagliari, Italy.
authors: Maria-Eliana
authors: ME
authors: Lai
authors: Ospedale Regionale per le Microcitemie, ASL8, Cagliari, Italy.
authors: Stefania
authors: S
authors: Vacquer
authors: Ospedale Regionale per le Microcitemie, ASL8, Cagliari, Italy.
authors: Renzo
authors: R
authors: Galanello
mesh_terms: D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D000095022:Interferon Lambda
chemical_list: D004247:DNA; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda