Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

被引：31

作者：

Cavanillas, M. L. ^{[1
]}

Fernandez, O. ^{[2
]}

Comabella, M. ^{[3
]}

Alcina, A. ^{[4
]}

Fedetz, M. ^{[4
]}

Izquierdo, G. ^{[5
]}

Lucas, M. ^{[6
]}

Cenit, M. C. ^{[1
]}

Arroyo, R. ^{[7
]}

Vandenbroeck, K. ^{[8
,9
]}

Alloza, I. ^{[8
]}

Garcia-Barcina, M. ^{[10
]}

Antigueedad, A. ^{[11
]}

Leyva, L. ^{[12
]}

Gomez, C. L. ^{[2
]}

Olascoaga, J. ^{[13
]}

Otaegui, D. ^{[14
]}

Blanco, Y. ^{[15
,16
]}

Saiz, A. ^{[15
,16
]}

Montalban, X. ^{[3
]}

Matesanz, F. ^{[4
]}

Urcelay, E. ^{[1
]}

机构：

[1] Hosp Clin S Carlos, Dept Immunol, Madrid, Spain

[2] Hosp Carlos Haya, Inst Neurociencias Clin, Malaga, Spain

[3] HUVH, Unitat Neuroimmunol Clin, CEM Cat, Ctr Esclerosi Multiple Catalunya, Barcelona, Spain

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

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

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

[7] Hosp Clin S Carlos, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain

[8] Univ Pais Vasco UPV EHU, Neurogenom Grp, Leioa, Spain

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

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

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

[12] Hosp Civil, Lab Invest, Malaga, Spain

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

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

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

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

来源：

GENES AND IMMUNITY | 2011年 / 12卷 / 02期

关键词：

multiple sclerosis; genetics; GWAS; GPC5; SUSCEPTIBILITY; RISK; GENES; POLYMORPHISMS; CHALLENGE; GENETICS; PROGRESS; THERAPY; ALLELES; CD58;

D O I：

10.1038/gene.2010.52

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670 (DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1); rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477 (EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36); rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex-and age-matched controls. Only rs9523762 mapping in the GPC5 gene was significantly associated (G allele, P = 1.6 x 10(-5); odds ratio (95% confidence interval) = 1.23 (1.12-1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care. Genes and Immunity (2011) 12, 110-115; doi:10.1038/gene.2010.52; published online 14 October 2010

引用

页码：110 / 115

页数：6

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