IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population.

BACKGROUND: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not.

AIMS: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry.

METHODS: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers.

RESULTS: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group.

CONCLUSION: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.