The autoimmune disease-associated KIF5A, CD226 and SH2B3 gene variants confer susceptibility for multiple sclerosis

被引：78

作者：

Alcina, A. ^{[1
]}

Vandenbroeck, K. ^{[2
,3
]}

Otaegui, D. ^{[4
]}

Saiz, A. ^{[5
,6
]}

Gonzalez, J. R. ^{[7
]}

Fernandez, O. ^{[8
]}

Cavanillas, M. L. ^{[10
]}

Cenit, M. C. ^{[10
]}

Arroyo, R. ^{[10
]}

Alloza, I. ^{[2
]}

Garcia-Barcina, M. ^{[11
]}

Antigueedad, A. ^{[12
]}

Leyva, L. ^{[9
]}

Izquierdo, G. ^{[13
]}

Lucas, M. ^{[14
]}

Fedetz, M. ^{[1
]}

Pinto-Medel, M. J. ^{[9
]}

Olascoaga, J. ^{[15
]}

Blanco, Y. ^{[5
,6
]}

Comabella, M. ^{[16
]}

Montalban, X. ^{[16
]}

Urcelay, E. ^{[10
]}

Matesanz, F. ^{[1
]}

机构：

[1] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain

[2] Univ Basque Country, EHU, Neurogenomiks Grp, Leioa, Spain

[3] Basque Fdn Sci, IKERBASQUE, Bilbao, Spain

[4] Inst Invest Sanitaria Biodonostia, Area Neurociencias, San Sebastian, Spain

[5] Hosp Clin Barcelona, Neurol Serv, Barcelona, Spain

[6] Inst Invest Biomed Pi & Sunyer IDIBAPS, Barcelona, Spain

[7] Inst Municipal Invest Med, CIBERESP, Ctr Recerca Epidemiol Ambiental CREAL, E-08003 Barcelona, Spain

[8] Hosp Reg Univ Carlos Haya, Serv Neurol, Malaga, Spain

[9] Hosp Reg Univ Carlos Haya, Inst Neurociencias Clin, Lab Invest, Malaga, Spain

[10] Hosp Clin S Carlos, Dept Neurol & Immunol, Madrid, Spain

[11] Hosp Basurto, Serv Genet, Bilbao, Spain

[12] Hosp Basurto, Serv Neurol, Bilbao, Spain

[13] Hosp Virgen Macarena, Unidad Esclerosis Multiple, Seville, Spain

[14] Hosp Virgen Macarena, Serv Biol Mol, Seville, Spain

[15] Hosp Donostia, Unidad Esclerosis Multiple, Serv Neurol, San Sebastian, Spain

[16] Hosp Univ Vall Hebron, Unitat Neuroimmunol Clin, CEM Cat, Ctr Esclerosi Multiple Catalunya, Barcelona, Spain

来源：

GENES AND IMMUNITY | 2010年 / 11卷 / 05期

关键词：

multiple sclerosis (MS); rheumatoid arthritis (RA); type 1 diabetes (T1D); KIF5A; CD226; SH2B3; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; REPLICATION; LOCI; POLYMORPHISMS; METAANALYSIS; BANK1; POPULATIONS; PHENOTYPE;

D O I：

10.1038/gene.2010.30

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) have revealed that different diseases share susceptibility variants. Twelve single-nucleotide polymorphisms (SNPs) previously associated with different immune-mediated diseases in GWAS were genotyped in a Caucasian Spanish population of 2864 multiple sclerosis (MS) patients and 2930 controls. Three SNPs were found to be associated with MS: rs1678542 in KIF5A (P = 0.001, odds ratio (OR) = 1.13, 95% confidence interval (CI) = 1.05-1.23); rs3184504 in SH2B3 (P = 0.00001, OR = 1.19, 95% CI = 1.10-1.27) and rs763361 in CD226 (P = 0.00007, OR = 1.16, 95% CI 1.08-1.25). These variants have previously been associated with rheumatoid arthritis and type 1 diabetes. The SH2B3 polymorphism has additionally been associated with systemic lupus erythematosus. Our results, in addition to validating some of these loci as risk factors for MS, are consistent with shared genetic mechanisms underlying different immune-mediated diseases. These data may help to shape the contribution of each pathway to different disorders. Genes and Immunity (2010) 11, 439-445; doi: 10.1038/gene.2010.30; published online 27 May 2010

引用

页码：439 / 445

页数：7

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