Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn disease

被引：138

作者：

Wolf, N. ^{[1
]}

Quaranta, M. ^{[1
]}

Prescott, N. J. ^{[1
]}

Allen, M. ^{[1
]}

Smith, R. ^{[2
,3
]}

Burden, A. D. ^{[4
]}

Worthington, J. ^{[3
]}

Griffiths, C. E. M. ^{[2
]}

Mathew, C. G. ^{[1
]}

Barker, J. N. ^{[1
]}

Capon, F. ^{[1
]}

Trembath, R. C. ^{[1
]}

机构：

[1] Kings Coll London, Div Med & Mol Genet, London, England

[2] Univ Manchester, Manchester M13 9PL, Lancs, England

[3] Univ Manchester, Epidemiol Unit, Manchester M13 9PL, Lancs, England

[4] Western Infirm & Associated Hosp, Glasgow, Lanark, Scotland

来源：

JOURNAL OF MEDICAL GENETICS | 2008年 / 45卷 / 02期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1136/jmg.2007.053595

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: Psoriasis is an immune-mediated skin disorder that is inherited as a multifactorial trait. Linkage analyses have clearly mapped a primary disease susceptibility locus to the major histocompatibility complex (MHC) region on chromosome 6p21. More recently, whole-genome association studies have identified two non-MHC disease genes (IL12B and IL23R), both of which also confer susceptibility to Crohn disease (CD). Objective and methods: To ascertain the genetic overlap between these two inflammatory conditions further, we investigated 15 CD-associated loci in a psoriasis case-control dataset. Results: The analysis of 1256 patients and 2938 unrelated controls found significant associations for loci mapping to chromosomes 1q24 (rs12035082, p = 0.009), 6p22 (rs6908425, p = 0.00015) and 21q22 (rs2836754, p = 0.0003). Notably, the marker showing the strongest phenotypic effect (rs6908425) maps to CDKAL1, a gene also associated with type 2 diabetes. Conclusions: These results substantiate emerging evidence for a pleiotropic role for s genes that contribute to the pathogenesis of immune-mediated disorders.

引用

页码：114 / 116

页数：3

共 18 条

[1] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[2] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[3] An update on the genetics of psoriasis [J].

Capon, F ;

Trembath, RC ;

Barker, JN .

DERMATOLOGIC CLINICS, 2004, 22 (04) :339-+

[4] Searching for the major histocompatibility complex psoriasis susceptibility gene [J].

Capon, F ;

Munro, M ;

Barker, J ;

Trembath, R .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 118 (05) :745-751

[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] Psoriasis 1 - Pathogenesis and clinical features of psoriasis [J].

Griffiths, Christopher E. M. ;

Barker, Jonathan N. W. N. .

LANCET, 2007, 370 (9583) :263-271

[8]

LEE FI, 1990, AM J GASTROENTEROL, V85, P962

[9] Genomewide scan in German families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13 [J].

Lee, YA ;

Rüschendorf, F ;

Windemuth, C ;

Schmitt-Egenolf, M ;

Stadelmann, A ;

Nürnberg, G ;

Ständer, M ;

Wienker, TF ;

Reis, A ;

Traupe, H .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (04) :1020-1024

[10] Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan [J].

Nair, RP ;

Henseler, T ;

Jenisch, S ;

Stuart, P ;

Bichakjian, CK ;

Lenk, W ;

Westphal, E ;

Guo, SW ;

Christophers, E ;

Voorhees, JJ ;

Elder, JT .

HUMAN MOLECULAR GENETICS, 1997, 6 (08) :1349-1356

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