title: Copy number variations in multiple sclerosis and neuromyelitis optica.
abstract: OBJECTIVE
  To clarify the potential association of copy number variations (CNVs) with multiple sclerosis (MS) and neuromyelitis optica (NMO) in Japanese cases.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Deletion-type CNVs at specific TCR loci regions contribute to MS and NMO susceptibility.
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Shinya
authors: S
authors: Sato
authors: Department of Medical Chemistry, Kurume University School of Medicine, Kurume.
authors: Ken
authors: K
authors: Yamamoto
authors: Department of Neurological Therapeutics, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Takuya
authors: T
authors: Matsushita
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Noriko
authors: N
authors: Isobe
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Yuji
authors: Y
authors: Kawano
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Kyoko
authors: K
authors: Iinuma
authors: Department of Clinical Research, Hokkaido Medical Center, Hokkaido.
authors: Masaaki
authors: M
authors: Niino
authors: Sapporo Neurology Clinic, Hokkaido, Japan.
authors: Toshiyuki
authors: T
authors: Fukazawa
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Yuri
authors: Y
authors: Nakamura
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Mitsuru
authors: M
authors: Watanabe
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Tomomi
authors: T
authors: Yonekawa
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Katsuhisa
authors: K
authors: Masaki
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Satoshi
authors: S
authors: Yoshimura
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Hiroyuki
authors: H
authors: Murai
authors: Department of Neurological Therapeutics, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Ryo
authors: R
authors: Yamasaki
authors: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors: Jun-Ichi
authors: J
authors: Kira
mesh_terms: D000293:Adolescent; D000328:Adult; D051401:Aquaporin 4 / Q000276:immunology; D044466:Asian People; D002875:Chromosomes / Q000235:genetics; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009471:Neuromyelitis Optica / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D015203:Reproducibility of Results; D012307:Risk Factors; D016176:T-Lymphocyte Subsets
chemical_list: D051401:Aquaporin 4; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta