Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease

Variation 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.


Published in:
Proceedings Of The National Academy Of Sciences Of The United States Of America, 110, 51, 20705-20710
Year:
2013
Publisher:
Washington, Natl Acad Sciences
ISSN:
0027-8424
Laboratories:




 Record created 2014-01-09, last modified 2018-03-17


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