Human Genetics

, 118:466 | Cite as

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

  • 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
Original Investigation

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.

Supplementary material

439_2005_48_MOESM1_ESM.pdf (172 kb)
Supplementary material

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Cynthia Helms
    • 1
  • Nancy L. Saccone
    • 1
    • 3
  • Li Cao
    • 1
  • Jil A. Wright. Daw
    • 1
  • Kai Cao
    • 4
    • 7
  • Tony M. Hsu
    • 5
  • Patricia Taillon-Miller
    • 5
  • Shenghui Duan
    • 5
  • Derek Gordon
    • 2
  • Brandon Pierce
    • 1
  • Jurg Ott
    • 2
  • John Rice
    • 3
  • Marcelo A. Fernandez-Vina
    • 4
    • 7
  • Pui-Yan Kwok
    • 5
  • Alan Menter
    • 6
  • Anne M. Bowcock
    • 1
    • 5
  1. 1.Department of GeneticsWashington University School of MedicineSt. LouisUSA
  2. 2.Laboratory of Statistical GeneticsThe Rockeffer UniversityNew YorkUSA
  3. 3.Department of PsychiatryWashington University School of MedicineSt. LouisUSA
  4. 4.Oncology DepartmentGeorgetown University School of MedicineWashingtonUSA
  5. 5.Division of Dermatology, Department of MedicineWashington University School of MedicineSt. LouisUSA
  6. 6.Department of Internal Medicine, Division of DermatologyBaylor University Medical CenterDallasUSA
  7. 7.Department of Laboratory MedicineThe University of Texas M.D. Anderson, Cancer CenterHoustonUSA

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