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.
de Cid
Rafael
R
Genes and Disease Programme, Centre for Genomic Regulation (CRG) and Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), 08003 Barcelona, Spain.
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
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
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