Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease. Proc Natl Acad Sci U S A, 110(51): 20705-10 (2013).

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Title: Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease
Authors: Kulkarni S, Qi Y, O'hUigin C, Pereyra F, Ramsuran V, McLaren P, Fellay J, Nelson G, Chen H, Liao W, Bass S, Apps R, Gao X, Yuki Y, Lied A, Ganesan A, Hunt PW, Deeks SG, Wolinsky S, Walker BD, Carrington M.
Journal: Proc Natl Acad Sci U S A,110(51):20705-10 (2013)

Journal Impact Factor (I.F.): 9.423
Number of citations (Google Scholar): 40

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.

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Citation: Kulkarni S, Qi Y, O'hUigin C, Pereyra F, Ramsuran V, McLaren P, Fellay J, Nelson G, Chen H, Liao W, Bass S, Apps R, Gao X, Yuki Y, Lied A, Ganesan A, Hunt PW, Deeks SG, Wolinsky S, Walker BD, Carrington M. Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease Proc Natl Acad Sci U S A,110(51):20705-10 (2013).


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