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- Title
Copy number variations in multiple sclerosis and neuromyelitis optica.
- Authors
Sato, Shinya; Yamamoto, Ken; Matsushita, Takuya; Isobe, Noriko; Kawano, Yuji; Iinuma, Kyoko; Niino, Masaaki; Fukazawa, Toshiyuki; Nakamura, Yuri; Watanabe, Mitsuru; Yonekawa, Tomomi; Masaki, Katsuhisa; Yoshimura, Satoshi; Murai, Hiroyuki; Yamasaki, Ryo; Kira, Jun‐ichi
- Abstract
<bold>Objective: </bold>To clarify the potential association of copy number variations (CNVs) with multiple sclerosis (MS) and neuromyelitis optica (NMO) in Japanese cases.<bold>Methods: </bold>Genome-wide association analyses of CNVs among 277 MS patients, 135 NMO/NMO spectrum disorder (NMOSD) patients, and 288 healthy individuals as a discovery cohort, and among 296 MS patients, 76 NMO/NMOSD patients, and 790 healthy individuals as a replication cohort were performed using high-density single nucleotide polymorphism microarrays.<bold>Results: </bold>A series of discovery and replication studies revealed that most identified CNVs were 5 to 50kb deletions at particular T cell receptor (TCR) gamma and alpha loci regions. Among these CNVs, a TCR gamma locus deletion was found in 16.40% of MS patients (p = 2.44E-40, odds ratio [OR] = 52.6), and deletion at the TCR alpha locus was found in 17.28% of MS patients (p = 1.70E-31, OR = 13.0) and 13.27% of NMO/NMOSD patients (p = 5.79E-20, OR = 54.6). These CNVs were observed in peripheral blood T-cell subsets only, suggesting the CNVs were somatically acquired. NMO/NMOSD patients carrying the CNV tended to be seronegative for anti-aquaporin-4 antibody or had significantly lower titers than those without CNV.<bold>Interpretation: </bold>Deletion-type CNVs at specific TCR loci regions contribute to MS and NMO susceptibility.
- Subjects
ASIANS; CELL receptors; CHROMOSOMES; GENETIC polymorphisms; GENETICS; GENOMES; LONGITUDINAL method; MEMBRANE proteins; MULTIPLE sclerosis; GENETIC mutation; POLYMERASE chain reaction; RESEARCH evaluation; T cells; SEQUENCE analysis; NEUROMYELITIS optica
- Publication
Annals of Neurology, 2015, Vol 78, Issue 5, p762
- ISSN
0364-5134
- Publication type
journal article
- DOI
10.1002/ana.24511