Kulkarni, SmitaQi, YingO'Huigin, ColmPereyra, FlorenciaRamsuran, VeronMclaren, PaulFellay, JacquesNelson, GeorgeChen, HaoyanLiao, WilsonBass, SaraApps, RichardGao, XiaojiangYuki, YukoLied, AlexandraGanesan, AnuradhaHunt, Peter W.Deeks, Steven G.Wolinsky, StevenWalker, Bruce D.Carrington, Mary2014-01-092014-01-092014-01-09201310.1073/pnas.1312237110https://infoscience.epfl.ch/handle/20.500.14299/99179WOS:000328548600078Variation in the 3' untranslated region (3'UTR) of the HLA-C locus determines binding of the microRNA Hsa-miR-148a, resulting in lower cell surface expression of alleles that bind miR-148a relative to those alleles that escape its binding. The HLA-C 3'UTR variant was shown to associate with HIV control, but like the vast majority of disease associations in a region dense with causal candidates, a direct effect of HLA-C expression level on HIV control was not proven. We demonstrate that a MIR148A insertion/deletion polymorphism associates with its own expression levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3'UTR. These data illustrate a direct effect of HLA-C expression level on HIV control that cannot be attributed to other HLA loci in linkage disequilibrium with HLA-C and highlight the rich complexity of genetic interactions in human disease.text::journal::journal article::research article