Psoriasis is associated with a SNP haplotype of the corneodesmosin gene (CDSN)

Orrù, Sandro; Giuressi, Erika; Casula, M.; Loizedda, Annalisa; Murru, Raffaele; Mulargia, M; Masala, Mv; Cerimele, D; Zucca, Mariagrazia; Aste, Nicola; Biggio, P.; Carcassi, Carlo; Contu, L.

doi:10.1034/j.1399-0039.2002.600403.x

Cited by 26 publications

(23 citation statements)

References 35 publications

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“…Indeed, the CDSN gene, located in PSORS1, the major susceptibility locus for psoriasis type I, is a strong candidate for this disease (Allen et al, 1999;Jenish et al, 1999;Tazi-Anhini et al, 1999;Orru et al, 2002;Capon et al, 2003). Particular psoriasis-associated polymorphisms encoding variants of the glycine loops may alter CDSN adhesive properties and be involved in the pathophysiology of the disease.…”

Section: Resultsmentioning

confidence: 96%

Homo-Oligomerization of Human Corneodesmosin Is Mediated by Its N-Terminal Glycine Loop Domain

Caubet

Jonca

Lopez

et al. 2004

Journal of Investigative Dermatology

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Corneodesmosin (CDSN), a glycoprotein expressed during the late stages of epidermal differentiation, localizes in the extracellular core of upper desmosomes and of corneodesmosomes. Since it displays homophilic adhesive properties, CDSN is thought to reinforce cell-cell cohesion within the upper layers of the epidermis. CDSN presents two serine- and glycine-rich domains in its N- and C-terminus that may fold into highly flexible and adhesive secondary structures called glycine loops. We analyzed the importance of these domains in CDSN homophilic adhesion by producing full-length and truncated recombinant forms of the protein deleted of the N- and/or the C-terminal domain. The adhesive properties of the various proteins were then tested in vitro by overlay binding assays and surface plasmon resonance quantitative analysis. Experiments evidenced the homophilic adhesive properties of the N-terminal glycine loop domain, confirming its involvement in CDSN-CDSN interactions. They further indicated that most of the C-terminal domain is not necessary for the adhesive properties of the protein. The dissociation constant (K(D)) was calculated to be 1.3x10(-5) M. This interaction strength might allow dynamic regulation of the CDSN-CDSN association to occur in vivo. Moreover, molecular filtration analyses demonstrated for the first time that non-glycosylated CDSN is able to spontaneously form large homo-oligomers in vitro and that the N-terminal glycine loop domain is necessary for the formation of these macromolecular complexes.

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Section: Resultsmentioning

confidence: 96%

Homo-Oligomerization of Human Corneodesmosin Is Mediated by Its N-Terminal Glycine Loop Domain

Caubet

Jonca

Lopez

et al. 2004

Journal of Investigative Dermatology

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“…In this regard, the dimorphic AluyTF is likely to be more strongly associated with one or other of the alleles of the neighboring TFIIH or CDSN genes rather than the alleles of the HLA-B, HLA-C or HLA-A genes that are found much further away. Interestingly, CDSN is a highly polymorphic gene with some haplotypes having a putative association with the skin disease, psoriasis [34,35]. Our future investigations will now focus on the relationship between the CDSN, TFIIH and the AluyTF polymorphisms in skin disease, and the distribution of polymorphic Alu haplotypes within the MHC class I region of different world populations.…”

Section: Discussionmentioning

confidence: 96%

Dimorphic Alu element located between the TFIIH and CDSN genes within the major histocompatibility complex

2003

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Most Alu members of the large SINE family are fixed within the human genome but some younger mobile members are dimorphic, that is, they are either present or absent in the genome. Four different dimorphic Alu insertions have been identified and characterized previously within the class I region of the major histocompatibility complex (MHC). Here we report on (i) the identification and characterization of a new dimorphic Alu insertion, AluyTF, located between the transcription factor II H (TFIIH) and corneodesmosin (CDSN) genes within a region of the MHC that is telomeric of the human leukocyte antigen type B (HLA-B) locus and centromeric of the HLA-A locus, (ii) the haplotypic relationships between the AluyTF dimorphism and the HLA-A and -B loci within a panel of 48 IHW cell-lines representing at least 36 different HLA class I haplotypes, (iii) the AluyTF genotype, allele and haplotype frequencies present in the Australian caucasian and Japanese populations, and (iv) the frequency of association between the AluTF dimorphisms and HLA-A and -B alleles in 108 Australian caucasians and 99 Japanese. The AluyTF insertion was present at 27% in the IHW cell lines, and the gene frequency was 0.107 and 0.083 in the Australian caucasian and Japanese population, respectively. The Alu haplotype frequencies constructed from four different dimorphic Alu loci including AluyTF within the MHC were not significantly different (p > 0.05) between the two populations. There were no significant associations between the Alu insertion and either the HLA-A or -B alleles except for a moderately strong association with HLA-A29 in the Australians (71.7%). This polymorphic AluyTF element, along with the four other previously described polymorphic Alu elements within the class I region of the MHC, will be useful lineage and linkage markers in human population studies and for elucidating the evolution of HLA class I haplotypes.

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“…The possible role of HLA-Cw6 in conferring susceptibility to Ps may be explained with its physiological role of presenting peptide antigens to the immune system, while in the case of CDSN a structural alteration of the corneodesmosin protein could be related with a possible role in initiating the pathologic process (8). Although clear differences have been found among the populations studied, both HLA class I and II alleles have been associated with PsA.…”

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confidence: 77%