Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

Background

To treat viral infection of chronic hepatitis C (CHC) is a main strategy to prevent progression of liver disease, and cancer. Some patients with CHC have failed to respond to the common antiviral therapy in different populations.

Objectives

In the current study it was aimed to find out the possible role of multiple drug resistance gene1 (MDR1) in non-responder patients with CHC infection in Turkish population.

Patients and Methods

Peripheral blood-EDTA samples were used for total genomic DNA isolation. In total of 55 patients with chronic hepatitis C and positive results for genotype 1 [31 male (56.4%), 24 female (43.6%) and mean age-min-max; 56.9 ± 9.66 (39-71)]; 19 responder (34.5%), 21 non responder (38.2%), and 15 recurrence (27.3%) were included in the presented results. Functional MDR1 gene was genotyped by multiplex PCR-based reverse-hybridization Strip Assay method, and some samples were confirmed by direct sequencing.

Results

Our results indicate that MDR1 gene polymorphism is strongly associated with non-responder patients and those with recurrent chronic hepatitis C during conventional drug therapy when compared to the responder patients. Homozygous of the TT genotype for MDR1 exon 26 polymorphism was at 2.0-fold higher risk of non-responder than patients with CC and CT.

Conclusions

The homozygous MDR1 3435TT genotype which encodes the xenobiotic transporter P-glycoprotein may be associated with a poor antiviral response in HCV chronicity during conventional therapy, and large-scale studies are needed to validate this association.