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 DRB104 or a locus included in the DRB104 haplotype, with AQP4 MS, which excluded DRB115:01. This study is the largest study of the HLA's contribution to MS in Japanese individuals.
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