title: SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients.
abstract: Although several major histocompatibility complex (MHC)-wide single-nucleotide polymorphism (SNP) studies have been performed in populations of European descent, none have been performed in Asian populations. The objective of this study was to identify human leukocyte antigen (HLA) loci associated with multiple sclerosis (MS) in a Japanese population genotyped for 3534 MHC region SNPs. Using a logistic regression model, two SNPs (MHC Class III SNP rs422951 in the NOTCH4 gene and MHC Class II SNP rs3997849, susceptible alleles A and G, respectively) were independently associated with MS susceptibility (204 patients; 280 controls), two (MHC Class II SNP rs660895 and MHC Class I SNP rs2269704 in the NRM gene, susceptible alleles G and G, respectively) with aquaporin-4- (AQP4-) MS susceptibility (149 patients; 280 controls) and a single SNP (MHC Class II SNP rs1694112, susceptible allele G) was significant when contrasting AQP4+ against AQP4- patients. Haplotype analysis revealed a large susceptible association, likely DRB1*04 or a locus included in the DRB1*04 haplotype, with AQP4- MS, which excluded DRB1*15:01. This study is the largest study of the HLA's contribution to MS in Japanese individuals.
authors.affiliation: Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA. Joseph.P.McElroy@gmail.com
authors.forename: J P
authors.initials: JP
authors.lastname: McElroy
authors.forename: N
authors.initials: N
authors.lastname: Isobe
authors.forename: P A
authors.initials: PA
authors.lastname: Gourraud
authors.forename: S J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Kohriyama
authors.forename: K
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatsuji
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: S L
authors.initials: SL
authors.lastname: Hauser
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: J
authors.initials: J
authors.lastname: Kira
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006680:HLA Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D006680:HLA Antigens; D059811:HLA-DRB1 Chains