title: Both the HLA-CPB1 and -DRB1 alleles correlate with risk for multiple sclerosis in Japanese: clinical phenotypes and gender as important factors.
abstract: The purpose of this study was to clarify the association of HLA-DRB1 and -DPB1 alleles with multiple sclerosis (MS) in Japanese, to determine whether optico-spinal MS (OS-MS) and conventional MS are immunogenetically distinct, and to verify the role of gender difference in HLA associations of MS. We studied HLA-DRB1 and -DPB1 polymorphisms in 166 Japanese patients with MS. Forty-seven patients were classified as having the optico-spinal MS (OS-MS) and 119 as having conventional MS. A lack of DPB1*0301 and a higher frequency of DPB1*0501 compared with controls (corrected P<0.0074; odds ratio=9.48) were found in OS-MS. By contrast, we found for the first time an association of DPB1*0301 with conventional MS in Japanese (corrected P=0.0444; odds ratio=3.28). Logistic analysis, adjusted for sex and age, revealed independent associations of DPB1*0301 (P=0.0004, adjusted odds ratio (aOR)=4.70), DPB1*0501 (P=0.0081, aOR= 2.50) and DRB1*1501 (P=0.0252, aOR=2.21) with conventional MS. However, the frequencies of DRB1*1501 and DPB1*0501 in male patients with conventional MS were equal to those in male controls while the DPB1*0301 frequency was increased in both male and female patients. We did not find any association of these HLA alleles with disease course and severity. In conclusion, OS-MS is a DPB1*0501-associated distinct subtype of MS, and DPB1*0301 is the most strongly associated allele with conventional MS in Japanese. In addition, gender plays an important role in HLA association with MS.
authors.affiliation: Hokuyukai Neurology Hospital, Sapporo, Japan. fukazawa@my.email.ne.jp
authors.forename: T
authors.initials: T
authors.lastname: Fukazawa
authors.forename: K
authors.initials: K
authors.lastname: Yamasaki
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Kikuchi
authors.forename: M
authors.initials: M
authors.lastname: Minohara
authors.forename: I
authors.initials: I
authors.lastname: Horiuchi
authors.forename: E
authors.initials: E
authors.lastname: Tsukishima
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Hamada
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Tashiro
authors.forename: J
authors.initials: J
authors.lastname: Kira
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency; D006682:HLA-DP Antigens / Q000235:genetics* / Q000276:immunology; D059868:HLA-DP beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D009471:Neuromyelitis Optica / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D010641:Phenotype; D012306:Risk; D012737:Sex Factors
chemical_list: D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains