The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8 þ and CD4 þ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; B30%) compared to Caucasian Americans (CA; B50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-a-2a and ribavirin. We observed carriage of A*02 (RR ¼ 1.33(1.08-1.64); P ¼ 0.008), B *58 (RR ¼ 1.84(1.24-2.73); P ¼ 0.002) and DPB1*1701 (RR ¼ 1.57(1.09-2.26); P ¼ 0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

We have investigated the association of multiple sclerosis (MS) with polymorphisms in the IL4R gene in 332 single-case MS families. IL4R encodes a subunit of the interleukin-4 receptor, a molecule important for T-cell development and differentiation, and is a gene shown to be associated with immune-related diseases such as asthma and type I diabetes. By genotyping two promoter and eight coding IL4R SNPs and identifying haplotypes (complex alleles) in the MS families, stratified for HLA genotype, we have observed evidence of the association of the IL4R gene to MS. In particular, we have identified a specific susceptibility haplotype, and observe that the risk is conferred primarily to individuals not carrying the high MS-risk HLA DR2 (DRB1*1501-DQB1*0602) haplotype (nominal P ¼ 0.009). These findings suggest a potentially important role for the IL4R gene in predisposition to MS, and provide further evidence of its relevance as a candidate gene for immune-related diseases.