Replication of LCE3C-LCE3B CNV as a Risk Factor for Psoriasis and Analysis of Interaction with Other Genetic Risk Factors

被引：59

作者：

Hueffmeier, Ulrike ^{[1
]}

Bergboer, Judith G. M. ^{[2
]}

Becker, Tim ^{[3
]}

Armour, John A. ^{[4
]}

Traupe, Heiko ^{[5
]}

Estivill, Xavier ^{[6
,7
,8
]}

Riveira-Munoz, Eva ^{[6
,7
]}

Moessner, Rotraut ^{[9
]}

Reich, Kristian ^{[10
]}

Kurrat, Werner ^{[11
]}

Wienker, Thomas F. ^{[3
]}

Schalkwijk, Joost ^{[2
]}

Zeeuwen, Patrick L. J. M. ^{[2
]}

Reis, Andre ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany

[2] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands

[3] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany

[4] Univ Nottingham, Inst Genet, Nottingham NG7 2RD, England

[5] Univ Munster, Dept Dermatol, D-4400 Munster, Germany

[6] Biomed Res Ctr CIBERESP, Publ Hlth & Epidemiol Network, Barcelona, Spain

[7] Ctr Genom Regulat CRG, Barcelona, Spain

[8] Pompeu Fabra Univ UPF, Barcelona, Spain

[9] Univ Gottingen, Dept Dermatol, Gottingen, Germany

[10] Dermatologikum, Hamburg, Germany

[11] Asklepios Nordseeklin, Westerland Sylt, Germany

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2010年 / 130卷 / 04期

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; POLYMORPHISMS; VARIANTS; VULGARIS; IL12B; IL23R; SCAN; IDENTIFICATION; CONFIRMS;

D O I：

10.1038/jid.2009.385

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Recently, a deletion of two late cornified envelope (LCE) genes within the epidermal differentiation complex on chromosome 1 was shown to be overrepresented in 1,426 psoriasis vulgaris (PsV) patients of European ancestry. In this study, we report a confirmation of this finding in 1,354 PsV patients and 937 control individuals of German origin. We found an allele frequency of the deletion of 70.9% in PsV patients and of 64.9% in control individuals (chi(2) = 17.44, P = 2.97 x 10(-5), odds ratio (95% confidence interval) 1.31 (1.15- 1.48)). The overall copy number of the two LCE genes had no influence on the age of onset, but we observed a dosage effect at the genotype level. There was no evidence of statistically significant interaction with copy number of the beta-defensin cluster on 8p23.1 or with an IL-23R pathway variant in a combined data set of German and Dutch individuals, whereas evidence for interaction with the PSORS1 risk allele in German individuals was marginal and did not remain significant after correction for multiple testing. Our study confirms the recently published finding that the deletion of the two LCE genes is a susceptibility factor for PsV with dosage effect, while, because of power limitation, no final conclusion regarding interaction with other PsV risk factors can be made at this stage.

引用

页码：979 / 984

页数：6

共 25 条

[1] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[2] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[3] Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis [J].

Capon, F ;

Helms, C ;

Veal, CD ;

Tillman, D ;

Burden, AD ;

Barker, JN ;

Bowcock, AM ;

Trembath, RC .

JOURNAL OF MEDICAL GENETICS, 2004, 41 (06) :459-460

[4] Searching for psoriasis susceptibility genes in Italy: Genome scan and evidence for a new locus on chromosome 1 [J].

Capon, F ;

Novelli, G ;

Semprini, S ;

Clementi, M ;

Nudo, M ;

Vultaggio, P ;

Mazzanti, C ;

Gobello, T ;

Botta, A ;

Fabrizi, G ;

Dallapiccola, B .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 112 (01) :32-35

[5] Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis [J].

Capon, Francesca ;

Di Meglio, Paola ;

Szaub, Joanna ;

Prescott, Natalie J. ;

Dunster, Christina ;

Baumber, Laura ;

Gutin, Alexander ;

Abkevic, Victor ;

Burden, A. David ;

Lanchbury, Jerry ;

Barker, Jonathan N. ;

Trembath, Richard C. ;

Nestle, Frank O. .

HUMAN GENETICS, 2007, 122 (02) :201-206

[6] A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes [J].

Cargill, Michele ;

Schrodi, Steven J. ;

Chang, Monica ;

Garcia, Veronica E. ;

Brandon, Rhonda ;

Callis, Kristina P. ;

Matsunami, Nori ;

Ardlie, Kristin G. ;

Civello, Daniel ;

Catanese, Joseph J. ;

Leong, Diane U. ;

Panko, Jackie M. ;

McAllister, Linda B. ;

Hansen, Christopher B. ;

Papenfuss, Jason ;

Prescott, Stephen M. ;

White, Thomas J. ;

Leppert, Mark F. ;

Krueger, Gerald G. ;

Begovich, Ann B. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (02) :273-290

[7] Cytokine gene polymorphisms in Chinese patients with psoriasis [J].

Chang, Y. T. ;

Chou, C. T. ;

Yu, C. W. ;

Lin, M. W. ;

Shiao, Y. M. ;

Chen, C. C. ;

Huang, C. H. ;

Lee, D. D. ;

Liu, H. N. ;

Wang, W. J. ;

Tsai, S. F. .

BRITISH JOURNAL OF DERMATOLOGY, 2007, 156 (05) :899-905

[8] Association of Skin Barrier Genes within the PSORS4 Locus Is Enriched in Singaporean Chinese with Early-Onset Psoriasis [J].

Chen, Huijia ;

Toh, Terry K. L. ;

Szeverenyi, Ildiko ;

Ong, Rick T. H. ;

Theng, Colin T. S. ;

McLean, W. H. Irwin ;

Seielstad, Mark ;

Lane, E. Birgitte .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (03) :606-614

[9] A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data:: Application to HLA in type 1 diabetes [J].

Cordell, HJ ;

Clayton, DG .

AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (01) :124-141

[10] Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis [J].

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 ;

Escaramis, Georgia ;

Ballana, Ester ;

Martin-Ezquerra, Gemma ;

den Heijer, Martin ;

Kamsteeg, Marijke ;

Joosten, Irma ;

Eichler, Evan E. ;

Lazaro, Conxi ;

Pujol, Ramon M. ;

Armengol, Lluis ;

Abecasis, Goncalo ;

Elder, James T. ;

Novelli, Giuseppe ;

Armour, John A. L. ;

Kwok, Pui-Yan ;

Bowcock, Anne ;

Schalkwijk, Joost ;

Estivill, Xavier .

NATURE GENETICS, 2009, 41 (02) :211-215

← 1 2 3 →