Gene-gene interaction and RNA splicing profiles of MAP2K4 gene in rheumatoid arthritis

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Klementy ShchetynskyL Padyukov

Abstract

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.

References

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Citations

Jun 7, 2017·PLoS Computational Biology·Mattias FrånbergBengt Sennblad
Oct 1, 2018·Annals of the Rheumatic Diseases·Kwangwoo Kim
Mar 20, 2019·Pediatric Hematology and Oncology·Niloofar NaderiAzam Bolhassani
Oct 10, 2021·Annals of the Rheumatic Diseases·Alejandro Ibáñez-CostaChary Lopez-Pedrera

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