title: Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease.
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.
authors.affiliation: 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.
authors.forename: Smita
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Colm
authors.initials: C
authors.lastname: O'hUigin
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Veron
authors.initials: V
authors.lastname: Ramsuran
authors.forename: Paul
authors.initials: P
authors.lastname: McLaren
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: George
authors.initials: G
authors.lastname: Nelson
authors.forename: Haoyan
authors.initials: H
authors.lastname: Chen
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
authors.forename: Sara
authors.initials: S
authors.lastname: Bass
authors.forename: Richard
authors.initials: R
authors.lastname: Apps
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yuki
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lied
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesan
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000276:immunology; D000483:Alleles; D001483:Base Sequence; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015236:HLA-C Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D054643:INDEL Mutation; D015810:Linkage Disequilibrium; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
chemical_list: D020413:3' Untranslated Regions; D015236:HLA-C Antigens; C550570:MIRN148 microRNA, human; D035683:MicroRNAs