Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis by de Cid Rafael, Riveira-Munoz Eva, Zeeuwen Patrick L J M, Robarge Jason, Liao Wilson, Dannhauser Emma N, Giardina Emiliano, Stuart Philip E, Nair Rajan, Helms Cynthia, Escaramís Georgia, Ballana Ester, Martín-Ezquerra Gemma, den Heijer Martin, Kamsteeg Marijke, Joosten Irma, Eichler Evan E, Lázaro Conxi, Pujol Ramón M, Armengol Lluís, Abecasis Gonçalo, Elder James T, Novelli Giuseppe, Armour John A L, Kwok Pui-Yan, Bowcock Anne, Schalkwijk Joost, Estivill Xavier in Nature genetics (2009).

[PMID: 19169253] PubMed


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.

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