MDR1 gene C3435T polymorphism in chronic hepatitis C patients.

BACKGROUND: MDR1 is a highly polymorphic gene that encodes P-glycoprotein (P-gp). This protein anchor to the cell membrane and transports toxins, xenobiotic, chemicals, and drugs from the intracellular to extracellular and thus protect cells. Polymorphism of the MDR1 gene seems to be effective in gene expression and response to treatment. Since one of the main mechanisms of drug resistance is the removal of the drug from the cell by ATP-dependent efflux proteins, thus MDR1, single nucleotide polymorphism (SNP) C3435T can be used as a predictor for treatment outcomes.

METHODS: The peripheral blood-EDTA samples were collected from 71 patients with chronic hepatitis C. The total genomic DNA extraction was carried out. The PCR was performed for detection of the MDR1 gene in HCV patients and MDR1 gene polymorphism was genotyped by the PCR-RFLP method.

RESULTS: Out of 71 patients 52 (73.3%) were male, 19 (26.7%) female with mean age-min-max; 41.17 ± 8.3-(26-59). The distribution of MDR1 genotype in 48(67.6%) responders were CC 13 (27%), CT 34 (71%) and TT 1(2%), while MDR1 genotypes in 8 (11.3%) non responders were CC 2(25%), CT 1(12.5%) TT 5(62.5%) and in 15(21.1%) recurrence were 5 (33%) CC, 6 (40%) CT and 4 (27%) TT genotype. The patients with heterozygous CT (C3435T) genotype 34/48(71%) were found better response than non-responders with TT 5/8(62.5%) genotype (p < 0.05).

CONCLUSION: Our result reveals that 71% of the responders were CT genotypes (C3435T) and 62.5% of non-responders were TT genotype (T3435T). With aforementioned results, determination of different forms of SNPs in MDR1 gene should be considered as a predictor in the treatment of all chronic HCV patients. The homozygous TT genotype and high prevalence of T allele may be related to low antiviral response during combined therapy in treatment of chronic HCV patients.