Influence of HLA-DRB1 alleles on the susceptibility and resistance to multiple sclerosis in Japanese patients with respect to anti-aquaporin 4 antibody status.

Journal article

BACKGROUND: Epistatic interactions between human leukocyte antigen (HLA)-DRB1 alleles alter multiple sclerosis (MS) risk in Caucasians. Such interactions have never been studied in Asian MS patients. OBJECTIVE: To investigate the influence of HLA-DRB1 alleles, including epistatic interactions at this locus, in Japanese MS patients with and without the anti-aquaporin 4 (AQP4) antibody. METHODS: The HLA-DRB1 locus was genotyped in 108 MS patients and 127 healthy controls. MS patients were further classified into two groups according to anti-AQP4 antibody status (27 positive and 81 negative). RESULTS: HLA-DRB1*09 (adjusted odds ratio (OR) = 0.243, 95% confidence interval (CI) 0.099-0.533) and HLA-DRB1*01 (adjusted OR = 0.327, 95% CI 0.103-0.873) decreased the incidence of anti-AQP4 antibody-negative MS. By contrast, HLA-DRB1*12 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 3.691, 95% CI 1.233-10.565). Individuals with HLA-DRB1*09/15 decreased the risk of anti-AQP4 antibody-negative MS (adjusted OR = 0.164, 95% CI 0.026-0.593), while those with HLA-DRB1*12/15 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 10.870, 95% CI 2.004-81.752). CONCLUSIONS: The ability of HLA-DRB1*09 to reduce the risk of anti-AQP4 antibody-negative MS may arise from an interaction with HLA-DRB1*15. By contrast, HLA-DRB1*12 increases susceptibility to anti-AQP4 antibody-positive MS, possibly via an interaction with HLA-DRB1*15.

Authors: Isobe, N; Matsushita, T; Yamasaki, R; Ramagopalan, S; Kawano, Y

• Publication status: Published
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England)
• Volume: 16
• Issue: 2
• Pages: 147-155
• Publication date: 2010-02-01
• DOI: 10.1177/1352458509355067
• EISSN: 1477-0970
• ISSN: 1352-4585
• Language: English
• Keywords: Odds Ratio; Risk Factors; Asian Continental Ancestry Group; Risk Assessment; Phenotype; Epistasis, Genetic; HLA-DRB1 Chains; Genetic Predisposition to Disease; Multiple Sclerosis, Relapsing-Remitting; Autoantibodies; Gene Frequency; Humans; Japan; Logistic Models; Aquaporin 4; Case-Control Studies; HLA-DR Antigens