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Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves’ disease and Hashimoto’s thyroiditis in the Japanese population
Human Immunology ( IF 3.1 ) Pub Date : 2020-12-30 , DOI: 10.1016/j.humimm.2020.12.007
Masahito Katahira 1 , Hidetada Ogata 2 , Hiromi Takashima 2 , Takahiro Ito 2 , Yuichi Hodai 3 , Tsutomu Miwata 3 , Megumi Goto 2 , Mariko Yamaguchi 2 , Akira Mizoguchi 2 , Mitsuhiro Kawakubo 4 , Shizuka Nakamura 2
Affiliation  

The effects of amino acid variants encoded by human leukocyte antigen (HLA) class II on the development of Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) have not been fully elucidated. We investigated the HLA-DRB1 genes of 243 GD patients and 82 HT patients in the Japanese population and compared the frequencies of HLA-DRB1 alleles and HLA-DRB1 amino acid variants between these patients and the Japanese populations previously reported by another institution. The frequencies of HLA-DRB1*04:05 and -DRB1*14:03 alleles were significantly higher and those of HLA-DRB1*01:01 and -DRB1*15:02 alleles were lower in GD patients than in controls. The frequencies of HLA-DRB1*08:03 and -DRB1*09:01 alleles were significantly higher and that of the HLA-DRB1*13:02 allele was lower in HT patients than in controls. A blind association analysis with all amino acid positions identified DRß9 and DRß31 for GD and DRß9, DRß13, and DRß21 for HT. The frequency of Glu-9 was significantly higher and that of Cys-9 was lower in GD patients than in controls. The frequencies of Lys-9 and Phe-13 were significantly higher in HT patients than in controls. DRß9 and DRß13 could be critical amino acid positions in the development of GD and HT.



中文翻译:

HLA-DRB1 同种异型中的关键氨基酸变异在日本人群中格雷夫斯病和桥本甲状腺炎的发展中

人类白细胞抗原 (HLA) II 类编码的氨基酸变体对格雷夫斯病 (GD) 和桥本甲状腺炎 (HT) 发展的影响尚未完全阐明。我们调查了日本人群中 243 名 GD 患者和 82 名 HT 患者的HLA-DRB1基因,并比较了这些患者与另一机构先前报告的日本人群之间HLA-DRB1等位基因和 HLA-DRB1 氨基酸变异的频率。GD患者HLA-DRB1*04:05-DRB1*14:03等位基因频率明显高于对照组,HLA-DRB1*01:01-DRB1*15:02等位基因频率低于对照组。的频率HT 患者的HLA-DRB1*08:03-DRB1*09:01等位基因显着高于对照组,而HLA-DRB1*13:02等位基因的显着低于对照组。对所有氨基酸位置的盲关联分析确定了 GD 的 DRß9 和 DRß31,HT 的 DRß9、DRß13 和 DRß21。与对照组相比,GD 患者中 Glu-9 的频率明显较高,而 Cys-9 的频率较低。Lys-9 和 Phe-13 的频率在 HT 患者中显着高于对照组。DRß9 和 DRß13 可能是 GD 和 HT 发展中的关键氨基酸位置。

更新日期:2020-12-30
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