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Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis.

ABSTRACT: Psoriasis is a common inflammatory skin disease with a prevalence of 2-3% in individuals of European ancestry. In a genome-wide search for copy number variants (CNV) using a sample pooling approach, we have identified a deletion comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene cluster. The absence of LCE3B and LCE3C (LCE3C_LCE3B-del) is significantly associated (P = 1.38E-08) with risk of psoriasis in 2,831 samples from Spain, The Netherlands, Italy and the United States, and in a family-based study (P = 5.4E-04). LCE3C_LCE3B-del is tagged by rs4112788 (r(2) = 0.93), which is also strongly associated with psoriasis (P < 6.6E-09). LCE3C_LCE3B-del shows epistatic effects with the HLA-Cw6 allele on the development of psoriasis in Dutch samples and multiplicative effects in the other samples. LCE expression can be induced in normal epidermis by skin barrier disruption and is strongly expressed in psoriatic lesions, suggesting that compromised skin barrier function has a role in psoriasis susceptibility.

SUBMITTER: de Cid R

PROVIDER: S-EPMC3128734 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis.

de Cid Rafael R Riveira-Munoz Eva E Zeeuwen Patrick L J M PL Robarge Jason J Liao Wilson W Dannhauser Emma N EN Giardina Emiliano E Stuart Philip E PE Nair Rajan R Helms Cynthia C Escaramís Georgia G Ballana Ester E Martín-Ezquerra Gemma G den Heijer Martin M Kamsteeg Marijke M Joosten Irma I Eichler Evan E EE Lázaro Conxi C Pujol Ramón M RM Armengol Lluís L Abecasis Gonçalo G Elder James T JT Novelli Giuseppe G Armour John A L JA Kwok Pui-Yan PY Bowcock Anne A Schalkwijk Joost J Estivill Xavier X

Nature genetics 20090125 2

Psoriasis is a common inflammatory skin disease with a prevalence of 2-3% in individuals of European ancestry. In a genome-wide search for copy number variants (CNV) using a sample pooling approach, we have identified a deletion comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene cluster. The absence of LCE3B and LCE3C (LCE3C_LCE3B-del) is significantly associated (P = 1.38E-08) with risk of psoriasis in 2,831 samples from Spain, The Netherlands, Italy and the United St ...[more]

PMID: 19169253

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Project description:PurposePsoriasis is a common cutaneous disease with multiple characteristics including inflammation and aberrant keratinocyte proliferation. However, the pathogenesis of psoriasis is not completely clear yet. The objective of this study is to perform an in-depth analysis of the association between SPRR and LCE in the pathogenesis of psoriasis.MethodsIn this study, we explore the differentially expressed genes (DEGs) in psoriasis by analyzing different gene expression profiles obtained from the Gene Expression Omnibus (GEO) database. The DEGs were examined using gene ontology (GO) functional enrichment analysis and protein-protein interactions (PPI) network. Correlation analysis in R studio software was used to analyze the association between SPRR and LCE genes. Further, potential direct protein-protein interactions between SPRR proteins and LCE3D were verified by co-localization observations and co-immunoprecipitation (CO-IP) assays in 293T cells. Also, the expression levels of SPRR and LCE genes were detected in lesional skin of the IMQ-induced psoriasiform dermatitis mice using RT-PCR.ResultsInterestingly, the small proline-rich (SPRR) and late cornified envelope (LCE) genes were identified as a module in the constructed PPI network. And the analysis of the gene expression profile GSE63684 showed that both SPRR family and LCE family genes were significantly upregulated in imiquimod (IMQ) induced psoriasiform dermatitis mice. Also, the correlation analysis in R studio software recognized the association of SPRR and LCE genes, which were further verified by co-localization and co-immunoprecipitation (CO-IP) assays in 293T cells, and the results show that the direct interactions between SPRR2 and LCE3D. Notably, we also found that the expression levels of SPRR and LCE genes were significantly increased in the IMQ-induced psoriasiform dermatitis mice, while specifically decreased under the tazarotene cream treatment, indicating that the SPRR and LCEs were regulated simultaneously in psoriasis.ConclusionIn summary, our study found that interactions between SPRR proteins and LCE proteins may provide new insights into the pathogenesis of psoriasis.

Dataset Information

Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis.

Publications

Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis.

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