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Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20705-10. doi: 10.1073/pnas.1312237110. Epub 2013 Nov 18.

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

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1
Cancer and Inflammation Program, Laboratory of Experimental Immunology and Basic Research Program, Center for Cancer Research Genetics Core, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702.

Abstract

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.

PMID:
24248364
PMCID:
PMC3870724
DOI:
10.1073/pnas.1312237110
[Indexed for MEDLINE]
Free PMC Article

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