RT Journal Article
T1 Fine mapping and functional analysis of the multiple sclerosis risk gene CD6.
A1 Swaminathan, Bhairavi
A1 Cuapio, Angélica
A1 Alloza, Iraide
A1 Matesanz, Fuencisla
A1 Alcina, Antonio
A1 García-Barcina, Maria
A1 Fedetz, Maria
A1 Fernández, Oscar
A1 Lucas, Miguel
A1 Orpez, Teresa
A1 Pinto-Medel, M Jesus
A1 Otaegui, David
A1 Olascoaga, Javier
A1 Urcelay, Elena
A1 Ortiz, Miguel A
A1 Arroyo, Rafael
A1 Oksenberg, Jorge R
A1 Antigüedad, Alfredo
A1 Tolosa, Eva
A1 Vandenbroeck, Koen
K1 Esclerosis múltiple
K1 estudio de asociación genómica completa
K1 Polimorfismo genético
K1 Timocitos
K1 Haplotipos
AB CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2(nd) SRCR domain with susceptibility to MS (P max(T) permutation = 1×10(-4)). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. - CD4(+) naïve cells, P = 0.0001; CD8(+) naïve cells, P<0.0001; CD4(+) and CD8(+) central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4(+) and CD8(+) T cells.
PB Public Library of Science
YR 2013
FD 2013-04-24
LK http://hdl.handle.net/10668/1362
UL http://hdl.handle.net/10668/1362
LA en
NO Swaminathan B, Cuapio A, Alloza I, Matesanz F, Alcina A, García-Barcina M, et al. Fine mapping and functional analysis of the multiple sclerosis risk gene CD6. PLoS ONE. 2013; 8(4):e62376
NO Journal Article;
DS RISalud
RD Apr 19, 2025