Interleukin 7 receptor a chain (IL7R) shows allelic and functional association with multiple sclerosis

被引：480

作者：

Gregory, Simon G.

Schmidt, Silke

Seth, Puneet

Oksenberg, Jorge R.

Hart, John

Prokop, Angela

Caillier, Stacy J.

Ban, Maria

Goris, An

Barcellos, Lisa F.

Lincoln, Robin

McCauley, Jacob L.

Sawcer, Stephen J.

Compston, D. A. S.

Dubois, Benedicte

Hauser, Stephen L.

Garcia-Blanco, Mariano A.

Pericak-Vance, Margaret A.

Haines, Jonathan L.

机构：

[1] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37232 USA

[2] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Ctr RNA Biol, Durham, NC 27710 USA

[4] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

[5] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[6] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England

[7] Katholieke Univ Leuven, Sect Expt Neurol, B-3000 Louvain, Belgium

[8] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA

[9] Univ Miami, Sch Med, Miami Inst Human Genom, Miami, FL 33136 USA

来源：

NATURE GENETICS | 2007年 / 39卷 / 09期

基金：

英国医学研究理事会;

关键词：

SINGLE-NUCLEOTIDE POLYMORPHISMS; THYMIC STROMAL LYMPHOPOIETIN; FAMILY-BASED TESTS; GENE-EXPRESSION; LINKAGE DISEQUILIBRIUM; DISEASE; IDENTIFICATION; RISK; SUSCEPTIBILITY; HOMEOSTASIS;

D O I：

10.1038/ng2103

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor a chain ( IL7R) as a significant risk factor for multiple sclerosis in four independent family- based or case- control data sets ( overall P 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane- bound isoforms of the protein by putatively disrupting an exonic splicing silencer.

引用

收藏

页码：1083 / 1091

页数：9

相关论文

共 51 条

[41] Multiple sclerosis severity score -: Using disability and disease duration to rate disease severity [J].

Roxburgh, RHSR ;

Seaman, SR ;

Masterman, T ;

Hensiek, AE ;

Sawcer, SJ ;

Vukusic, S ;

Achiti, I ;

Confavreux, C ;

Coustans, M ;

le Page, E ;

Edan, G ;

McDonnell, GV ;

Hawkins, S ;

Trojano, M ;

Liguori, M ;

Cocco, E ;

Marrosu, MG ;

Tesser, F ;

Leone, MA ;

Weber, A ;

Zipp, F ;

Miterski, B ;

Epplen, JT ;

Oturai, A ;

Sorensen, PS ;

Celius, EG ;

Lara, NT ;

Montalban, X ;

Villoslada, P ;

Silva, AM ;

Marta, M ;

Leite, I ;

Dubois, B ;

Rubio, J ;

Butzkueven, H ;

Kilpatrick, T ;

Mycko, MP ;

Selmaj, KW ;

Rio, ME ;

Sá, M ;

Salemi, G ;

Savettieri, G ;

Hillert, J ;

Compston, DAS .

NEUROLOGY, 2005, 64 (07) :1144-1151

[42] Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis [J].

Schmidt, S. ;

Pericak-Vance, M. A. ;

Sawcer, S. ;

Barcellos, L. F. ;

Hart, J. ;

Sims, J. ;

Prokop, A. M. ;

van der Walt, J. ;

DeLoa, C. ;

Lincoln, R. R. ;

Oksenberg, J. R. ;

Compston, A. ;

Hauser, S. L. ;

Haines, J. L. ;

Gregory, S. G. .

GENES AND IMMUNITY, 2006, 7 (05) :384-392

[43] Haplotype association analysis of discrete and continuous traits using mixture of regression models [J].

Sham, PC ;

Rijsdijk, FV ;

Knight, J ;

Makoff, A ;

North, B ;

Curtis, D .

BEHAVIOR GENETICS, 2004, 34 (02) :207-214

[44] IDENTIFICATION OF MURINE LOCI ASSOCIATED WITH SUSCEPTIBILITY TO CHRONIC EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS [J].

SUNDVALL, M ;

JIRHOLT, J ;

YANG, HT ;

JANSSON, L ;

ENGSTROM, A ;

PETTERSSON, U ;

HOLMDAHL, R .

NATURE GENETICS, 1995, 10 (03) :313-317

[45] Identification of 11 novel and common single nucleotide polymorphisms in the interleukin-7 receptor-α gene and their associations with multiple sclerosis [J].

Teutsch, SM ;

Booth, DR ;

Bennetts, BH ;

Heard, RNS ;

Stewart, GJ .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2003, 11 (07) :509-515

[46] IL-7-enhanced T-cell response to myelin proteins in multiple sclerosis [J].

Traggiai, E ;

Biagioli, T ;

Rosati, E ;

Ballerini, C ;

Mazzanti, B ;

Ben Nun, A ;

Massacesi, L ;

Vergelli, M .

JOURNAL OF NEUROIMMUNOLOGY, 2001, 121 (1-2) :111-119

[47] Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions [J].

van Horssen, J. ;

Vos, C. M. P. ;

Admiraal, L. ;

van Haastert, E. S. ;

Montagne, L. ;

van der Valk, P. ;

de Vries, H. E. .

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2006, 32 (06) :585-593

[48] Twin concordance and sibling recurrence rates in multiple sclerosis [J].

Willer, CJ ;

Dyment, DA ;

Risch, NJ ;

Sadovnick, AD ;

Ebers, GC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) :12877-12882

[49] SNPselector:: a web tool for selecting SNPs for genetic association studies [J].

Xu, H ;

Gregory, SG ;

Hauser, ER ;

Stenger, JE ;

Pericak-Vance, MA ;

Vance, JM ;

Züchner, S ;

Hauser, MA .

BIOINFORMATICS, 2005, 21 (22) :4181-4186

[50] EXACT TESTS FOR ASSOCIATION BETWEEN ALLELES AT ARBITRARY NUMBERS OF LOCI [J].

ZAYKIN, D ;

ZHIVOTOVSKY, L ;

WEIR, BS .

GENETICA, 1995, 96 (1-2) :169-178

← 1 2 3 4 5 6 →