Novel association of the CD226 (DNAM-1) Gly307Ser polymorphism in Wegener's granulomatosis and confirmation for multiple sclerosis in German patients

被引：68

作者：

Wieczorek, S. ^{[1
]}

Hoffjan, S. ^{[1
]}

Chan, A. ^{[2
]}

Rey, L. ^{[1
]}

Harper, L. ^{[3
]}

Fricke, H. ^{[4
]}

Holle, J. U. ^{[5
,6
]}

Gross, W. L. ^{[5
,6
]}

Epplen, J. T. ^{[1
]}

Lamprecht, P. ^{[5
,6
]}

机构：

[1] Ruhr Univ Bochum, D-44780 Bochum, Germany

[2] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, D-44780 Bochum, Germany

[3] Univ Birmingham, Wellcome Trust Clin Res Facil, Div Immun & Infect, Birmingham, W Midlands, England

[4] Apogenix GmbH, Heidelberg, Germany

[5] Med Univ Lubeck, Dept Rheumatol, Vasculitis Ctr UKSH, D-23538 Lubeck, Germany

[6] Med Univ Lubeck, Klinikum Bad Bramstedt, D-23538 Lubeck, Germany

来源：

GENES AND IMMUNITY | 2009年 / 10卷 / 06期

关键词：

Wegener's granulomatosis; multiple sclerosis; genetics; CD226; association; T-CELLS; SYSTEMIC VASCULITIS; CHROMOSOME; 6P21.3; LYMPHOCYTES; GENE; REMISSION; FREQUENCY; EXPANSION; REGION; BLOOD;

D O I：

10.1038/gene.2009.44

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Recently, there has been increasing evidence that a non-synonymous exchange (Gly307Ser) in the gene for CD226 is linked to several autoimmune diseases including type 1 diabetes, multiple sclerosis ( MS), rheumatoid arthritis and Grave's disease. Here we present evidence that this polymorphism also predisposes to Wegener's granulomatosis (WG), an autoimmune condition belonging to the group of ANCA (antineutrophil cytoplasmic autoantibody)-associated vasculitides. We found a significant association of the 307Ser allele in separate panels of 520 Northern German ( P = 0.016, odds ratio (OR) = 1.20) and 122 Southern German (P = 0.020, OR = 1.37) WG cases compared with 1226 healthy controls. The importance of this single-nucleotide polymorphism in the etiopathology of ANCA-associated vasculitides is supported by similar effect sizes that we found in British WG cases (n = 105) and German patients with Churg-Strauss syndrome ( n 119), which, however, miss significance level because of the relatively small cohorts available for these rare disorders. Finally, we confirm the association with MS in a cohort of 422 German patients ( P = 0.011, OR = 1.23). Genes and Immunity ( 2009) 10, 591-595; doi:10.1038/gene.2009.44; published online 18 June 2009

引用

页码：591 / 595

页数：5

共 36 条

[1]

Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission [J].

Abdulahad, Wayel H. ;

Stegeman, Coen A. ;

Limburg, Pieter C. ;

Kallenberg, Cees G. A. .

ARTHRITIS AND RHEUMATISM, 2008, 58 (07) :2196-2205

[2]

Functional defect of circulating regulatory CD4+T cells in patients with Wegener's granulomatosis in remission [J].

Abdulahad, Wayel H. ;

Stegeman, Coen A. ;

van der Geld, Ymke M. ;

Doornbos-van der Meer, Berber ;

Limburg, Pieter C. ;

Kallenberg, Cees G. M. .

ARTHRITIS AND RHEUMATISM, 2007, 56 (06) :2080-2091

[3]

The expanding genetic overlap between multiple sclerosis and type I diabetes [J].

Booth, David R. ;

Heard, Robert N. ;

Stewart, Graeme J. ;

Goris, An ;

Dobosi, Rita ;

Dubois, Benedicte ;

Lorentzen, Aslaug R. ;

Celius, Elisabeth G. ;

Harbo, Hanne F. ;

Spurkland, Anne ;

Olsson, Tomas ;

Kockum, Ingrid ;

Link, Jenny ;

Hillert, Jan ;

Ban, Maria ;

Baker, Amie ;

Sawcer, Stephen ;

Compston, Alastair ;

Mihalova, Tania ;

Strange, Richard ;

Hawkins, Clive ;

Ingram, Gillian ;

Robertson, Neil P. ;

De Jager, Philip L. ;

Hafler, David A. ;

Barcellos, Lisa F. ;

Ivinson, Adrian J. ;

Pericak-Vance, Margaret ;

Oksenberg, Jorge R. ;

Hauser, Stephen L. ;

McCauley, Jacob L. ;

Sexton, David ;

Haines, Jonathan .

GENES AND IMMUNITY, 2009, 10 (01) :11-14

[4]

Expansion of circulating NKG2D+ effector memory T-cells and expression of NKG2D-ligand MIC in granulomaous lesions in Wegener's granulomatosis [J].

Capraru, Dorin ;

Mueller, Antje ;

Csernok, Elena ;

Gross, Wolfgang L. ;

Holl-Ulrich, Konstanze ;

Northfield, John ;

Klenerman, Paul ;

Herlyn, Karen ;

Holle, Julia ;

Gottschlich, Stefan ;

Voswinkel, Jan ;

Spies, Thomas ;

Fagin, Ursula ;

Jabs, Wolfram J. ;

Lamprecht, Peter .

CLINICAL IMMUNOLOGY, 2008, 127 (02) :144-150

[5]

CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions [J].

Dardalhon, V ;

Schubart, AS ;

Reddy, J ;

Meyers, JH ;

Monney, L ;

Sabatos, CA ;

Ahuja, R ;

Nguyen, K ;

Freeman, GJ ;

Greenfield, EA ;

Sobel, RA ;

Kuchroo, VK .

JOURNAL OF IMMUNOLOGY, 2005, 175 (03) :1558-1565

[6]

Elishmereni M, 2008, CURR OPIN INVEST DR, V9, P491

[7]

ALPHA1-ANTITRYPSIN GENETIC-POLYMORPHISM IN ANCA-POSITIVE SYSTEMIC VASCULITIS [J].

ESNAULT, VLM ;

TESTA, A ;

AUDRAIN, M ;

ROGE, C ;

HAMIDOU, M ;

BARRIER, JH ;

SESBOUE, R ;

MARTIN, JP ;

LESAVRE, P .

KIDNEY INTERNATIONAL, 1993, 43 (06) :1329-1332

[8]

FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity [J].

Fanciulli, Manuela ;

Norsworthy, Penny J. ;

Petretto, Enrico ;

Dong, Rong ;

Harper, Lorraine ;

Kamesh, Lavanya ;

Heward, Joanne M. ;

Gough, Stephen C. L. ;

de Smith, Adam ;

Blakemore, Alexandra I. F. ;

Owen, Catherine J. ;

Pearce, Simon H. S. ;

Teixeira, Luis ;

Guillevin, Loic ;

Graham, Deborah S. Cunninghame ;

Pusey, Charles D. ;

Cook, H. Terence ;

Vyse, Timothy J. ;

Aitman, Timothy J. .

NATURE GENETICS, 2007, 39 (06) :721-723

[9]

Sample size requirements for association studies of gene-gene interaction [J].

Gauderman, WJ .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 2002, 155 (05) :478-484

[10]

Gencik M, 1999, CLIN EXP IMMUNOL, V117, P412

← 1 2 3 4 →