Open AccessIdentification 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(s) -
Ryosuke Tashiro,
Kuniyasu Niizuma,
SeikSoon Khor,
Katsushi Tokunaga,
Miki Fujimura,
Hiroyuki Sakata,
Hidenori Endo,
Hidetoshi Inoko,
Kunio Ogasawara,
Teiji Tominaga
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0220858
Subject(s) - human leukocyte antigen , haplotype , allele , immunology , odds ratio , medicine , allele frequency , thyroiditis , haplotype estimation , genotype , graves' disease , genetics , disease , biology , antigen , gene
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.