A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2003-12

AUTHORS

Cynthia Helms, Li Cao, James G Krueger, Ellen M Wijsman, Francesca Chamian, Derek Gordon, Michael Heffernan, Jil A Wright Daw, Jason Robarge, Jurg Ott, Pui-Yan Kwok, Alan Menter, Anne M Bowcock

ABSTRACT

Psoriasis (OMIM 177900) is a chronic inflammatory skin disorder of unknown pathogenesis affecting approximately 2% of the Western population. It occurs more frequently in individuals with human immunodeficiency virus, and 20-30% of individuals with psoriasis have psoriatic arthritis. Psoriasis is associated with HLA class I alleles, and previous linkage analysis by our group identified a second psoriasis locus at 17q24-q25 (PSORS2; ref. 7). Linkage to this locus was confirmed with independent family sets. Additional loci have also been proposed to be associated with psoriasis. Here we describe two peaks of strong association with psoriasis on chromosome 17q25 separated by 6 Mb. Associated single-nucleotide polymorphisms (SNPs) in the proximal peak lie in or near SLC9A3R1 (also called EBP50 and NHERF1) and NAT9, a new member of the N-acetyltransferase family. SLC9A3R1 is a PDZ domain-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family and is implicated in diverse aspects of epithelial membrane biology and immune synapse formation in T cells. The distal peak of association is in RAPTOR (p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats). Expression of SLC9A3R1 is highest in the uppermost stratum Malpighi of psoriatic and normal skin and in inactive versus active T cells. A disease-associated SNP lying between SLC9A3R1 and NAT9 leads to loss of RUNX1 binding. This is the second example of loss of a RUNX1 binding site associated with susceptibility to an autoimmune disease. It also suggests defective regulation of SLC9A3R1 or NAT9 by RUNX1 as a susceptibility factor for psoriasis. More... »

PAGES

349-356

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1268

DOI

http://dx.doi.org/10.1038/ng1268

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044083260

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/14608357


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Download the RDF metadata as:  json-ld nt turtle xml License info

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RDF/XML is a standard XML format for linked data.

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