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SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients

Genes & Immunity volume 12, pages 523–530 (2011)Cite this article

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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.

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Acknowledgements

We thank the MS patients and controls who participated in this study. We thank RR Lincoln, R Guerrero, H Mousavi and A Santaniello for sample and database management. This work was supported by grants from the National Institute of Health U19AI067152, RO1NS46297 and National Multiple Sclerosis Society RG3060C8. JPM is a post-doctoral fellow supported by the National MS Society. NI is a post-doctoral fellow supported by The Association for Preventive Medicine of Japan. The members of the South Japan Multiple Sclerosis Genetic Consortium are J Kira, N Isobe, T Matsushita and S Yoshimura (Kyushu University), S Kusunoki and K Miyamoto (Kinki University), S Sakoda and Y Nakatsuji (Osaka University), T Kohriyama, K Ochi and M Matsumoto (Hiroshima University), T Kanda (Yamaguchi University) and T Miki and Y Kawano (Ehime University).

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Authors and Affiliations

  1. Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA

    J P McElroy, P A Gourraud, S J Caillier, S L Hauser & J R Oksenberg

  2. Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    N Isobe & J Kira

  3. Department of Clinical Neuroimmunology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    T Matsushita

  4. Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan

    T Kohriyama

  5. Department of Neurology, Kinki University School of Medicine, Osaka, Japan

    K Miyamoto

  6. Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan

    Y Nakatsuji

  7. Department of Geriatric Medicine, Graduate School of Medicine, Ehime University, Ehime, Japan

    T Miki

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Correspondence to J P McElroy.

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McElroy, J., Isobe, N., Gourraud, P. et al. SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients. Genes Immun 12, 523–530 (2011). https://doi.org/10.1038/gene.2011.25

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