TY - JOUR
T1 - Identification of HLA-DRB1∗04:10 allele as risk allele for Japanese moyamoya disease and its association with autoimmune thyroid disease
T2 - A case-control study
AU - Tashiro, Ryosuke
AU - Niizuma, Kuniyasu
AU - Khor, Seik Soon
AU - Tokunaga, Katsushi
AU - Fujimura, Miki
AU - Sakata, Hiroyuki
AU - Endo, Hidenori
AU - Inoko, Hidetoshi
AU - Ogasawara, Koetsu
AU - Tominaga, Teiji
N1 - Funding Information:
This work was supported by Ministry of Health, Labour and Welfare (MHLW) Grant Number S17310031, Japan Agency for Medical Research and Development (AMED) Grant Number J170001344 and Japan Society for the promotion of Science (JSPS) KAKENHI Grant Number 17K10815. GenoDive Pharma Inc. provided support in the form of salaries for H. I., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.
Funding Information:
Funding:ThisworkwassupportedbyMinistryof Health,LabourandWelfare(MHLW)Grant NumberS17310031,JapanAgencyforMedical ResearchandDevelopment(AMED)GrantNumber J170001344andJapanSocietyforthepromotion ofScience(JSPS)KAKENHIGrantNumber 17K10815.GenoDivePharmaInc.provided supportintheformofsalariesforH.I.,butdidnot
Publisher Copyright:
© 2019 Tashiro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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 HLADPB1) 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.
AB - 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 HLADPB1) 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.
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U2 - 10.1371/journal.pone.0220858
DO - 10.1371/journal.pone.0220858
M3 - Article
C2 - 31412073
AN - SCOPUS:85070707769
VL - 14
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0220858
ER -