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A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.

Original publication

DOI

10.1126/science.1232685

Type

Journal article

Journal

Science

Publication Date

05/04/2013

Volume

340

Pages

87 - 91

Keywords

African Americans, Alleles, Amino Acid Sequence, Anti-Retroviral Agents, Crohn Disease, Gene Expression Regulation, HIV, HIV Infections, HLA-C Antigens, Humans, Immunodominant Epitopes, Molecular Sequence Data, Mutation, Peptide Fragments, Polymorphism, Single Nucleotide, T-Lymphocytes, Cytotoxic, Viral Load