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

被引：408

作者：

de Cid, Rafael ^{[1
,2
]}

Riveira-Munoz, Eva ^{[1
,2
]}

Zeeuwen, Patrick L. J. M. ^{[3
,4
]}

Robarge, Jason ^{[5
]}

Liao, Wilson ^{[6
]}

Dannhauser, Emma N. ^{[7
,8
]}

Giardina, Emiliano ^{[9
]}

Stuart, Philip E. ^{[10
]}

Nair, Rajan ^{[10
]}

Helms, Cynthia ^{[5
]}

Escaramis, Georgia ^{[1
,2
]}

Ballana, Ester ^{[1
,2
]}

Martin-Ezquerra, Gemma ^{[11
]}

den Heijer, Martin ^{[12
,13
]}

Kamsteeg, Marijke ^{[3
,4
]}

Joosten, Irma ^{[14
]}

Eichler, Evan E. ^{[15
]}

Lazaro, Conxi ^{[16
]}

Pujol, Ramon M. ^{[11
]}

Armengol, Lluis ^{[1
,2
]}

Abecasis, Goncalo ^{[17
]}

Elder, James T. ^{[10
]}

Novelli, Giuseppe ^{[9
]}

Armour, John A. L. ^{[7
,8
]}

Kwok, Pui-Yan ^{[6
]}

Bowcock, Anne ^{[5
]}

Schalkwijk, Joost ^{[3
,4
]}

Estivill, Xavier ^{[1
,2
,18
]}

机构：

[1] Ctr Gene Regulat, Genes & Dis Programme, Barcelona 08003, Spain

[2] Publ Hlth & Epidemiol Network Biomed Res Ctr CIBE, Barcelona 08003, Spain

[3] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, NL-6525 Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6525 Nijmegen, Netherlands

[5] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[6] Univ Calif San Francisco, San Francisco, CA 94143 USA

[7] Univ Nottingham, Inst Genet, Queens Med Ctr, Nottingham NG7 2RD, England

[8] Univ Nottingham, Sch Biol, Queens Med Ctr, Nottingham NG7 2RD, England

[9] Univ Roma Tor Vergata, Dept Biopathol, I-00133 Rome, Italy

[10] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

[11] Hosp del Mar, Dermatol Serv, IMAS, Barcelona 08003, Spain

[12] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 Nijmegen, Netherlands

[13] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6525 Nijmegen, Netherlands

[14] Radboud Univ Nijmegen, Med Ctr, Dept Bloodtransfus & Transplantat Immunol, NL-6525 Nijmegen, Netherlands

[15] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[16] Hosp Llobregat, Catalan Inst Canc, Barcelona 08907, Spain

[17] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA

[18] Pompeu Fabra Univ UPF, Barcelona 08003, Spain

来源：

NATURE GENETICS | 2009年 / 41卷 / 02期

关键词：

COPY NUMBER; STRUCTURAL VARIATION; HUMAN GENOME; ASSOCIATION; PATHOGENESIS; GENETICS; PSORS1; LOCUS; IL12B; IL23R;

D O I：

10.1038/ng.313

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Psoriasis is a common inflammatory skin disease with a prevalence of 2-3% in individuals of European ancestry(1). 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(2). 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.

引用

页码：211 / 215

页数：5

共 26 条

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