Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis
Copyright policy )Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis
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.
- University of Michigan–Ann Arbor United States
- Radboud University Nijmegen Netherlands
- University of Michigan–Flint United States
- University of Mary United States
- Amsterdam UMC Netherlands
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DNA; allele; article; contingent negative variation; controlled study; disease association; disease course; epidermis; family study; gene; gene cluster; gene deletion; gene disruption; gene expression; gene induction; genetic epistasis; genetic risk; genetic susceptibility; genome; human; human tissue; Italy; keratinocyte; lce3b gene; lce3c gene; major clinical study; Netherlands; priority journal; psoriasis; skin biopsy; Spain; United States; Case-Control Studies; Cornified Envelope Proline-Rich Proteins; Epistasis, Genetic; Europe; Family; Gene Deletion; Genetic Predisposition to Disease; Genetics, Population; Genome-Wide Association Study; Genotype; HLA-C Antigens; Humans; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Proteins; Psoriasis; United States, N4i 1: Pathogenesis and modulation of inflammation, genetic risk, gene cluster, Linkage Disequilibrium, genetic epistasi, NCMLS 2: Immune Regulation, NCMLS 1: Infection and autoimmunity, disease course, allele, article, Single Nucleotide, contingent negative variation, gene induction, Europe, Italy, priority journal, Case-Control Studie, gene disruption, United State, Genotype, Population, epidermi, keratinocyte, HLA-C Antigens, IGMD 6: Hormonal regulation, Polymorphism, Single Nucleotide, lce3b gene, Netherland, Genetic, Cornified Envelope Proline-Rich Proteins, Genetics, Humans, Psoriasis, controlled study, family study, Family, Genetic Predisposition to Disease, human, Internal Medicine - Radboud University Medical Center, Polymorphism, gene, genome, skin biopsy, psoriasi, gene deletion, HLA-C Antigen, lce3c gene, Protein, disease association, Proteins, Epistasis, Genetic, DNA, Cornified Envelope Proline-Rich Protein, NCEBP 1: Molecular epidemiology, major clinical study, human tissue, United States, Genetics, Population, ONCOL 3: Translational research, Spain, Case-Control Studies, gene expression, Epistasis, Gene Deletion, genetic susceptibility, Genome-Wide Association Study
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