Nature Genetics
35, 349 - 356 (2003)
Published online: 9 November 2003; | doi:10.1038/ng1268
A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasisCynthia Helms1, Li Cao1, James G Krueger2, Ellen M Wijsman3, Francesca Chamian2, Derek Gordon4, Michael Heffernan5, Jil A Wright Daw1, Jason Robarge1, Jurg Ott4, Pui-Yan Kwok6, Alan Menter7
& Anne M Bowcock1, 51
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. 2
Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10021, USA. 3
Division of Medical Genetics and Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA. 4
Lab of Statistical Genetics, The Rockefeller University, New York, New York 10021, USA. 5
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. 6
University of California, San Francisco, 505 Parnassus Ave, Long 1332A, Box 0130, San Francisco, California 94143-0130, USA. 7
Department of Internal Medicine, Division of Dermatology, Baylor University Medical Center, Dallas, Texas 75246, USA.
Correspondence should be addressed to Anne M Bowcock bowcock@genetics.wustl.eduPsoriasis (OMIM 177900) is a chronic inflammatory skin disorder of unknown pathogenesis affecting  2% of the Western population1. It occurs more frequently in individuals with human immunodeficiency virus2, and 20−30% of individuals with psoriasis have psoriatic arthritis3. Psoriasis is associated with HLA class I alleles4,
5,
6, 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 sets8,
9. Additional loci have also been proposed to be associated with psoriasis10. 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 cells11,
12. The distal peak of association is in RAPTOR (p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats)13,
14. 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 disease15. It also suggests defective regulation of SLC9A3R1 or NAT9 by RUNX1 as a susceptibility factor for psoriasis.
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