Gene-gene interaction and RNA splicing profiles of MAP2K4 gene in rheumatoid arthritis
Copyright © 2015. Published by Elsevier Inc.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 158(2015), 1 vom: 03. Mai, Seite 19-28 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2015
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Alternative splicing Gene–gene interaction MAP2K4 RNA expression Rheumatoid arthritis Epitopes HLA-DRB1 Chains RNA, Messenger mehr... |
| Zusammenfassung: | Copyright © 2015. Published by Elsevier Inc. We performed gene-gene interaction analysis, with HLA-DRB1 shared epitope (SE) alleles for 195 SNPs within immunologically important MAP2K, MAP3K and MAP4K gene families, in 2010 rheumatoid arthritis (RA) patients and 2280 healthy controls. We found a significant statistical interaction for rs10468473 with SE alleles in autoantibody-positive RA. Individuals heterozygous for rs10468473 demonstrated higher expression of total MAP2K4 mRNA in blood, compared to A-allele homozygous. We discovered a novel, putatively translated, "cassette exon" RNA splice form of MAP2K4, differentially expressed in peripheral blood mononuclear cells from 88 RA cases and controls. Within the group of RA patients, we observed a correlation of MAP2K4 isoform expression with carried SE alleles, autoantibody, and rheumatoid factor profiles. TNF-dependent modulation of isoform expression pattern was detected in the Jurkat cell line. Our data suggest a genetic interaction between MAP2K4 and HLA-DRB1, and the importance of rs10468473 and MAP2K4 splice variants in the development of autoantibody-positive RA |
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| Beschreibung: | Date Completed 07.07.2015 Date Revised 25.11.2016 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2015.02.011 |