Influence of HLA-C expression level on HIV control.
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.
Apps, R; Qi, Y; Carlson, JM; Chen, H; Gao, X; Thomas, R; Yuki, Y; Del Prete, GQ; Goulder, P; Brumme, ZL; Brumme, CJ; John, M; Mallal, S; Nelson, G; Bosch, R; Heckerman, D; Stein, JL; Soderberg, KA; Moody, MA; Denny, TN; Zeng, X; Fang, J; Moffett, A; Lifson, JD; Goedert, JJ; Buchbinder, S; Kirk, GD; Fellay, J; McLaren, P; Deeks, SG; Pereyra, F; Walker, B; Michael, NL; Weintrob, A; Wolinsky, S; Liao, W; Carrington, M
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