It is provided isolated polynucleotides that include sequences from genomic region around the gene CD 81. The polynucleotides include polymorphisms associated with treatment response of HCV patients to interferon-.alpha. and ribavirin combined therapy and are useful as the probes in screening for patients who will response to interferon-.alpha. and ribavirin combined therapy. It is further provided linkage disequilibrium structure of the CD81 gene and haplotype information within a particular LD block, which can be used for prediction of the treatment outcome of the interferon-.alpha. and ribavirin combined therapy on HCV patients.