Genetic variation at immunoglobulin kappa locus is associated with hepatitis C-treatment-induced viral clearance in African Americans

Host genetic factors, especially genes of the immune system, are thought to contribute to the racial differences in response rates to therapy for hepatitis C virus (HCV) infection. The aim of the present investigation was to determine whether immunoglobulin gamma heavy chain marker (GM) and kappa light chain marker (KM) -were associated with sustained viral response (SVR) in patients treated with peginterferon-α-2a and ribavirin. DNA samples from 319 subjects with genotype-1 HCV infections were allotyped for alleles at four GM loci: GM3/GM17, GM23+/GM23−, GM5/GM21, GM6+/GM6− and the KM locus: KM1/KM3, using molecular methods. Noncarriage of KM1 allele, i.e., KM3 homozygosity, was associated with higher SVR in African Americans (odds ratio = 2.50, 95% confidence interval = 1.12-5.60). Consistent with this finding, the HCV RNA level in KM1 noncarriers was significantly (p = 0.013) lower than in carriers of this allele. Thus, the KM3 allele may be a marker for higher SVR in African Americans.