Genetic interplay between<i>HLA-C</i>and<i>MIR148A</i>in HIV control and Crohn disease
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- Smita Kulkarni
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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- Ying Qi
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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- Colm O’hUigin
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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- Florencia Pereyra
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139;
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- Veron Ramsuran
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139;
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- Paul McLaren
- School of Life Sciences, École Polytechnique Fédérale de Lausanne and Institute of Microbiology, University of Lausanne, 1011 Lausanne, Switzerland;
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- Jacques Fellay
- School of Life Sciences, École Polytechnique Fédérale de Lausanne and Institute of Microbiology, University of Lausanne, 1011 Lausanne, Switzerland;
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- George Nelson
- Basic Research Program, Center for Cancer Research Genetics Core, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702;
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- Haoyan Chen
- Department of Dermatology, University of California, San Francisco, CA 94115;
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- Wilson Liao
- Department of Dermatology, University of California, San Francisco, CA 94115;
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- Sara Bass
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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- Richard Apps
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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- Xiaojiang Gao
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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- Yuko Yuki
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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- Alexandra Lied
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139;
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- Anuradha Ganesan
- Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD 20817;
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- Peter W. Hunt
- San Francisco General Hospital AIDS Division, University of California, San Francisco, CA 94110; and
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- Steven G. Deeks
- San Francisco General Hospital AIDS Division, University of California, San Francisco, CA 94110; and
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- Steven Wolinsky
- Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611
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- Bruce D. Walker
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139;
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- Mary Carrington
- Cancer and Inflammation Program, Laboratory of Experimental Immunology and
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説明
<jats:title>Significance</jats:title><jats:p>In the human population different<jats:italic>HLA-C</jats:italic>allotypes are present that have different expression levels at the cell surface. Individuals with higher expressed<jats:italic>HLA-C</jats:italic>allotypes demonstrate better HIV control but increased risk of Crohn disease. A microRNA, miR-148a, regulates expression of some HLA-C allotypes. We report here that this microRNA also varies in expression level between people.<jats:italic>MIR148A</jats:italic>variation showed significant and opposing effects on HIV viral control vs. risk of Crohn disease, specifically in subjects with<jats:italic>HLA-C</jats:italic>alleles that are regulated by miR-148a. These results are independent of confounding effects by other<jats:italic>HLA</jats:italic>loci because only HLA-C is regulated by miR-148a. Our data represent an example of gene interactions that affect immune response and thereby the risk of human disease.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 110 (51), 20705-20710, 2013-11-18
Proceedings of the National Academy of Sciences