PMID- 10332047
OWN - NLM
STAT- MEDLINE
DCOM- 19990708
LR  - 20191210
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 6
DP  - 1999 Jun
TI  - Novel genetic association between the corneodesmosin (MHC S) gene and 
      susceptibility to psoriasis.
PG  - 1135-40
AB  - Psoriasis is an inflammatory skin disease of unknown origin, but with a clear 
      genetic component. The strongest genetic association has been found with the 
      major histocompatibility complex (MHC) region, and specifically between 
      susceptibility to familial early onset psoriasis and human leukocyte antigen 
      (HLA)-Cw6. The basis of this association of the HLA-C locus with disease 
      pathogenesis is, however, not clear, and it is possible that other genes, or a 
      combination of genes, in the HLA region are of functional importance. The MHC S 
      gene is expressed specifically in keratinocyte differentiation and, being located 
      160 kb telomeric of HLA-C, is a plausible candidate gene. We analysed the allelic 
      distribution of two polymorphisms in the MHC S gene (at +619 and +1243) in a 
      case-control association study. We could confirm a significant association 
      between psoriasis and HLA-Cw6 [odds ratio (OR) = 7.75]. No association was found 
      between disease (or any subtypes) and the MHC S gene polymorphism at position 
      +619, despite its close proximity to HLA-C and the strong linkage disequilibrium 
      between the loci. However, a significant trend with the rarer allele at MHC S 
      (+1243) and psoriasis was detected in the overall data set (OR = 2. 66; P = 2 
      [times] 10(-)9). This effect was most pronounced in the type 1a (early onset) 
      psoriatics (OR = 3.43). Furthermore, homozygosity for the associated allele at 
      MHC S (+1243) increased the risk of disease over that for carriage of HLA-Cw6 
      alone (OR = 9. 38), suggesting that allele 2 of MHC S (+1243) provides an 
      additional risk in psoriasis susceptibility. The strong association found here, 
      coupled with the biological involvement of the MHC S gene product corneodesmosin 
      in skin physiology, implicates this locus (or a haplotype across HLA-C and MHC S 
      ) in the impaired desquamation characteristic of psoriasis.
FAU - Tazi Ahnini, R
AU  - Tazi Ahnini R
AD  - Division of Molecular and Genetic Medicine, University of Sheffield, Royal 
      Hallamshire Hospital, Sheffield S10 2JF, UK. r.taziahnini@shef.ac.uk
FAU - Camp, N J
AU  - Camp NJ
FAU - Cork, M J
AU  - Cork MJ
FAU - Mee, J B
AU  - Mee JB
FAU - Keohane, S G
AU  - Keohane SG
FAU - Duff, G W
AU  - Duff GW
FAU - di Giovine, F S
AU  - di Giovine FS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (CDSN protein, human)
RN  - 0 (Glycoproteins)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-C*06 antigen)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
SB  - IM
EIN - Hum Mol Genet 2000 Mar 1;9(4):659
MH  - Adult
MH  - Age of Onset
MH  - Alleles
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Glycoproteins/*genetics
MH  - HLA-C Antigens/genetics
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Linkage Disequilibrium
MH  - Male
MH  - Odds Ratio
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Psoriasis/*genetics/pathology
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - ddc129 [pii]
AID - 10.1093/hmg/8.6.1135 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Jun;8(6):1135-40. doi: 10.1093/hmg/8.6.1135.