A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis - PubMed (original) (raw)

Comparative Study

doi: 10.1038/ng1268. Epub 2003 Nov 9.

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

Affiliations

• PMID: 14608357
• DOI: 10.1038/ng1268

Comparative Study

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

Cynthia Helms et al. Nat Genet. 2003 Dec.

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.

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Comment in

• A RUNX trio with a taste for autoimmunity.
  Alarcón-Riquelme ME. Alarcón-Riquelme ME. Nat Genet. 2003 Dec;35(4):299-300. doi: 10.1038/ng1203-299. Nat Genet. 2003. PMID: 14647282 No abstract available.
• No association between atopic dermatitis and the SLC9A3R1-NAT9 RUNX1 binding site polymorphism in Japanese patients.
  Hosomi N, Fukai K, Oiso N, Kato A, Fukui M, Ishii M. Hosomi N, et al. Clin Exp Dermatol. 2005 Mar;30(2):192-3. doi: 10.1111/j.1365-2230.2005.01720.x. Clin Exp Dermatol. 2005. PMID: 15725257 No abstract available.

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