期刊
SCIENCE
卷 340, 期 6128, 页码 87-91出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1232685
关键词
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资金
- National Institutes of Health (NIH) [HHSN261200800001E, N02-CP-55504, RO1-AI046995, R01-DA04334, R01-DA12568, R01-AI060460]
- Bill & Melinda Gates Foundation [38599]
- Mark and Lisa Schwartz Foundation
- Wellcome Trust
- NIH National Institute of Allergy and Infectious Diseases (NIAID) Center for HIV/AIDS Vaccine Immunology [U01-AI-067854]
- Australian National Health and Medical Research Council [384702]
- National Institutes of Health [K08AR057763, R01-DA-04334, R01-DA-12568]
- Creative and Novel Ideas in HIV Research Program [P30 AI027767-24]
- Swiss National Science Foundation [33CSC0-108787]
- NIAID
- National Cancer Institute
- National Heart, Lung, and Blood Institute [UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]
- [RO1 AI087145]
- [K24AI069994]
- [P30 AI027763]
- [UL1 RR024131]
- [P30 MH62246]
- [R24 AI067039]
- British Heart Foundation [PG/09/077/27964] Funding Source: researchfish
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.
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