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

Smita Kulkarni, Ying Qi, Colm O'hUigin, Florencia Pereyra, Veron Ramsuran, Paul McLaren, Jacques Fellay, George Nelson, Haoyan Chen, Wilson Liao, Sara Bass, Richard Apps, Xiaojiang Gao, Yuko Yuki, Alexandra Lied, Anuradha Ganesan, Peter W. Hunt, Steven G. Deeks, Steven Wolinsky, Bruce D. WalkerMary Carrington*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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 ŒUTR 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.

Original languageEnglish (US)
Pages (from-to)20705-20710
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number51
DOIs
StatePublished - Dec 17 2013

ASJC Scopus subject areas

  • General

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