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PLoS One. 2019 Aug 14;14(8):e0220858. doi: 10.1371/journal.pone.0220858. eCollection 2019.

Identification of HLA-DRB1*04:10 allele as risk allele for Japanese moyamoya disease and its association with autoimmune thyroid disease: A case-control study.

Author information

1
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
2
Department of Immunobiology, Tohoku University Institute of Development, Aging and Cancer, Sendai, Japan.
3
Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
4
Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
5
Department of Human Genetics, the University of Tokyo Graduate School of Medicine, Tokyo, Japan.
6
Department of Neurosurgery, Kohnan Hospital, Sendai, Japan.
7
Genodive Pharma Inc., Atsugi, Kanagawa, Japan.

Abstract

BACKGROUND AND PURPOSE:

Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology. Growing evidence suggest its involvement of autoimmune and genetic mechanisms in the pathogenesis of MMD. This study aims to clarify the association between HLA allele and MMD.

METHODS:

Case-control study: the DNA of 136 MMD patients in Japan was extracted and the genotype of human leukocyte antigen (HLA) from this DNA was determined by super-high-resolution single-molecule sequence-based typing using next-generation sequencing. Next, the frequency of each HLA allele (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1) was compared with those in the Japanese control database. In addition, haplotype estimation was performed using the expectation maximization algorithm.

RESULTS:

The frequencies of the HLA-DRB1*04:10 allele (4.77% vs. 1.47% in the control group; P = 1.7 × 10-3; odds ratio [OR] = 3.35) and of the HLA-DRB1*04:10-HLA-DQB1*04:02 haplotype (haplotype frequency 4.41% vs. 1.35% in the control group; P = 2.0 × 10-3; OR = 3.37) significantly increased. The frequency of thyroid diseases, such as Graves' disease and Hashimoto thyroiditis, increased in HLA-DRB1*04:10-positive MMD patients compared with that in HLA-DRB1*04:10-negative MMD patients.

CONCLUSIONS:

HLA-DRB1*04:10 is a risk allele and HLA-DRB1*04:10-HLA-DQB1*04:02 a risk haplotype for MMD. In addition, HLA-DRB1*04:10 is associated with thyroid disease in MMD patients.

Conflict of interest statement

All authors have no conflict of interest related to our manuscript. H.I. is an employee of GenoDive Pharma Inc, and has financial supported from the company in the form of the salary. Other authors received no specific funding from any companies including Genodive Pharma Inc. H.I., played a role in study design and data analysis. Genodive Pahrma Inc. does not alter our adherence to PLOS ONE policies on sharing data and materials.

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