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
Genes and Disease Programme, Centre for Genomic Regulation (CRG) and Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), 08003 Barcelona, Spain.
Nat Genet. 2009 Feb;41(2):211-5. doi: 10.1038/ng.313. Epub 2009 Jan 25.
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.
银屑病是一种常见的炎症性皮肤病，在欧洲血统个体中的患病率为2%-3%。在一项使用样本池方法进行的全基因组拷贝数变异（CNV）搜索中，我们鉴定出一个包含晚期角质化包膜（LCE）基因簇成员LCE3B和LCE3C的缺失。在来自西班牙、荷兰、意大利和美国的2831个样本以及一项基于家系的研究中（P = 5.4E-04），LCE3B和LCE3C缺失（LCE3C_LCE3B-del）与银屑病风险显著相关（P = 1.38E-08）。LCE3C_LCE3B-del由rs4112788标记（r(2) = 0.93），其也与银屑病强烈相关（P < 6.6E-09）。在荷兰样本中，LCE3C_LCE3B-del对银屑病的发生显示出上位性效应，而在其他样本中显示出相乘效应。LCE表达可通过皮肤屏障破坏在正常表皮中诱导，并且在银屑病皮损中强烈表达，这表明受损的皮肤屏障功能在银屑病易感性中起作用。
