학술논문
Fine mapping and functional analysis of the multiple sclerosis risk gene CD6.
Document Type
article
Author
Bhairavi Swaminathan; Angélica Cuapio; Iraide Alloza; Fuencisla Matesanz; Antonio Alcina; Maria García-Barcina; Maria Fedetz; Oscar Fernández; Miguel Lucas; Teresa Orpez; M Jesus Pinto-Medel; David Otaegui; Javier Olascoaga; Elena Urcelay; Miguel A Ortiz; Rafael Arroyo; Jorge R Oksenberg; Alfredo Antigüedad; Eva Tolosa; Koen Vandenbroeck
Source
PLoS ONE, Vol 8, Iss 4, p e62376 (2013)
Subject
Language
English
ISSN
1932-6203
Abstract
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