Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin and HCR View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-12

AUTHORS

Cynthia Helms, Nancy L. Saccone, Li Cao, Jil A. Wright. Daw, Kai Cao, Tony M. Hsu, Patricia Taillon-Miller, Shenghui Duan, Derek Gordon, Brandon Pierce, Jurg Ott, John Rice, Marcelo A. Fernandez-Vina, Pui-Yan Kwok, Alan Menter, Anne M. Bowcock

ABSTRACT

Psoriasis is a complex inflammatory disease of the skin affecting 1-2% of the Caucasian population. Associations with alleles from the HLA class I region (now known as PSORS1), particularly HLA-Cw*0602, were described over 20 years ago. However, extensive linkage disequilibrium (LD) within this region has made it difficult to identify the true susceptibility allele from this region. A variety of genes and regions from a 238-kb interval extending from HLA-B to corneodesmosin (CDSN) have been proposed to harbor PSORS1. In order to identify the minimum block of LD in the MHC class I region associated with psoriasis we performed a comprehensive case/control and family-based association study on 242 Northern European psoriasis families and two separate European control populations. High resolution HLA typing of HLA-A, -B and -C alleles was performed, in addition to the genotyping of 18 polymorphic microsatellites and 36 SNPs from a 772-kb segment of the HLA class I region harboring the previously described interval. This corresponded on average to one SNP every 7 kb in the candidate 238 kb region. With all tests, the association was the strongest with single markers and haplotypes from a block of LD harboring HLA-C and SNP n.9. Logistic regression analyses indicated that association seen with candidate genes from the interval such as CDSN and HCR was entirely dependent on association with HLA-Cw*0602 and SNP n.9-G alleles. The previously reported association with CDSN and HCR was observed to be due to the existence of the associated alleles lying on the most commonly over-transmitted haplotype. Rare over-transmitted haplotypes also harbored HLA-Cw*12 alleles. HLA-Cw*12 family members are closely related to HLA Cw*0602, sharing identical sequences in their alpha-2 domains, peptide-binding pockets A, D and E and all 3' introns. The introduction of a potential binding site for the RUNX/AML family of transcription factors in intron 7, is also specific to these HLA-C alleles. These variants need to be investigated further for their role as PSORS1. More... »

PAGES

466

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-005-0048-2

DOI

http://dx.doi.org/10.1007/s00439-005-0048-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002786904

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16235096


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