title: 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.
authors.affiliation: Genes and Disease Programme, Centre for Genomic Regulation (CRG) and Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), 08003 Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Eva
authors.initials: E
authors.lastname: Riveira-Munoz
authors.forename: Patrick L J M
authors.initials: PL
authors.lastname: Zeeuwen
authors.forename: Jason
authors.initials: J
authors.lastname: Robarge
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
authors.forename: Emma N
authors.initials: EN
authors.lastname: Dannhauser
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
authors.forename: Philip E
authors.initials: PE
authors.lastname: Stuart
authors.forename: Rajan
authors.initials: R
authors.lastname: Nair
authors.forename: Cynthia
authors.initials: C
authors.lastname: Helms
authors.forename: Georgia
authors.initials: G
authors.lastname: Escaramís
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
authors.forename: Gemma
authors.initials: G
authors.lastname: Martín-Ezquerra
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Marijke
authors.initials: M
authors.lastname: Kamsteeg
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Conxi
authors.initials: C
authors.lastname: Lázaro
authors.forename: Ramón M
authors.initials: RM
authors.lastname: Pujol
authors.forename: Lluís
authors.initials: L
authors.lastname: Armengol
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Abecasis
authors.forename: James T
authors.initials: JT
authors.lastname: Elder
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: John A L
authors.initials: JA
authors.lastname: Armour
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Anne
authors.initials: A
authors.lastname: Bowcock
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
mesh_terms: D016022:Case-Control Studies; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D004843:Epistasis, Genetic / Q000502:physiology; D005060:Europe; D005190:Family; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*; D014481:United States
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; C524768:LCE3C protein, human; C484393:PSORS1C1 protein, human; D011506:Proteins