TORNA ALL’ELENCO

Relationship of genetic variations of the gene coding for the human equilibrative nucleoside transporter-1 (hENT1) with protein expression and response to treatment in chronic hepatitis C in Digestive and Liver Disease

2011
AO Ordine Mauriziano

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (23)Vedi tutti...

Tarabra E

Framarin L

Actis GC


et alii...

Abstract

Background and aim: Standard therapy for hepatitis C is PEG-IFN + Ribavirin (RBV). RBV can enter the cells through hENT1. A SNP at positions -706G>C in the proximal upstream region of hENT1 (rs747199) has been reported to have a role in the regulation of its expression and function. Our aim was to evaluate if the presence of rs747199C/G SNP correlates with 1) erythrocyte expression of hENT1 2) therapeutic response. Material and methods: 638 hepatitis C pts referring to the 7 participating centers and completing a full cycle of PEG-IFN +RBV plus a 6 mo FU have been enrolled. An interim analysis of the first 212 pts is reported. 37 genotype 1 pts have been analyzed hENT1 erythrocyte expression. HENT1 rs747199 was genotyped by real-time PCR. Erythrocyte hENT-1 protein expression was evaluated by western blot. Results: h-ENT1 erytrocyte expression: In the 21 NR pts significantly higher level of hENT-1 compared to the 16 SVR pts (NR=88.31±10.19 arbitrary units (AU); SVR = 37.96±10.39 AU; p=0.0034) has been observed. Although not significantly different, pts with CC genotype have lower hENT-1 expression levels (GG=69.47±10.80 AU vs CG=53.80±13.03 AU and CC=44.14±10.85 AU). CC genotype could therefore represent a predictor of response. h-ENT1 genotyping: 212 HCV pts have been analyzed (Mean age 47±2; M/F 112/100). Genotype 1&4: 172 pts (81%) (baseline viremia: mean 2.700.000±4.285.000 IU/ml - < 600.000 IU/ml: 60 pts (35%); SVR 68 (40%), NR & relapsers 104 (60%)). IL28b rs12979860 GG was detected in 4/172 (24%), rs8099917 TT in 88/172 (51%). Genotypes 2&3: 40 pts (19%) (baseline viremia: mean 3.764.000±8.272.000 IU/ml - < 600.000 IU/ml: 15 pts (37.5%), SVR 34 (85%), NR& relapsers 6 (15%)). IL28b rs12979860 GG was detected in 16/40 (40%), rs8099917 TT in 25/40 (62%). No significant correlation was observed between h-ENT1 rs747199 C/G and SVR even after stratification for viral genotype, viremia, age, gender, stage and IL28 genetic. Conclusions: 1) SVR is assoc

DOI : 10.1016/S1590-8658(11)60203-X

Keywords

equilibrative nucleoside transporter 1; ribavirin; health care organization; gastrointestinal disease; human; hepatitis C; protein expression; gene; genetic variability; genotype; viremia; erythrocyte; erythrocyte level; therapy; treatment response; real time polymerase chain reaction; Western blotting; stratification; gender;