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

Rafael De Cid, Eva Riveira-Munoz, Patrick L.J.M. Zeeuwen, Jason Robarge, Wilson Liao, Emma N. Dannhauser, Emiliano Giardina, Philip E. Stuart, Rajan Nair, Cynthia Helms, Georgia Escaramís, Ester Ballana, Gemma Martín-Ezquerra, Martin Den Heijer, Marijke Kamsteeg, Irma Joosten, Evan E. Eichler, Conxi Lázaro, Ramón M. Pujol, Lluís ArmengolGonçalo Abecasis, James T. Elder, Giuseppe Novelli, John A.L. Armour, Pui Yan Kwok, Anne Bowcock, Joost Schalkwijk, Xavier P. Estivill

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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 (r2 = 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.

Original languageEnglish
Pages (from-to)211-215
Number of pages5
JournalNature Genetics
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

De Cid, R., Riveira-Munoz, E., Zeeuwen, P. L. J. M., Robarge, J., Liao, W., Dannhauser, E. N., Giardina, E., Stuart, P. E., Nair, R., Helms, C., Escaramís, G., Ballana, E., Martín-Ezquerra, G., Heijer, M. D., Kamsteeg, M., Joosten, I., Eichler, E. E., Lázaro, C., Pujol, R. M., ... Estivill, X. P. (2009). Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nature Genetics, 41(2), 211-215. https://doi.org/10.1038/ng.313