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 e 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 associated with a significantly lower expression of h-ENT1 at erythrocyte level, 2) a lower h-ENT1 expression may be associated with h-ENT1 rs747199 CC genotype, but 3) CC genotype is not predictive of SVR
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
TARABRA, ELENA;BOCCA, Claudia;CIANCIO, Alessia;
2011-01-01
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 e 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 associated with a significantly lower expression of h-ENT1 at erythrocyte level, 2) a lower h-ENT1 expression may be associated with h-ENT1 rs747199 CC genotype, but 3) CC genotype is not predictive of SVR
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
