Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves’ disease and Hashimoto’s thyroiditis in the Japanese population

Katahira, Masahito; Ogata, Hiroyasu; Takashima, Hiromi; Ito, Takahiro; Hodai, Yuichi; Tsutomu, Miwata; Goto, Megumi; Yamaguchi, M.; Mizoguchi, Akira; Kawakubo, Mitsuhiro; Nakamura, Shizuka

doi:10.1016/j.humimm.2020.12.007

Cited by 9 publications

(22 citation statements)

References 33 publications

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“…In Korean population, DRB1*0301, DRB1*0802, DRB1*0803, and DRB1*1403 were found to be positively associated with GD [13,16]. In Japanese population, DRB1*0405, DRB1*1403, and DRB1*0803 were found to be positively associated with GD [14,15,18]. In Chinese population, DRB1*1602, and DRB1*0901 were found to be positively associated with GD [17,19,20].…”

Section: Introductionmentioning

confidence: 87%

“…More importantly, the most effective molecule at position 74 in Chinese population was DRβ1-Glu74, which has a strong protective effect against GD. And there is no allele encoding Arg at the HLA-DRB1 position 74 among HLA-DRβ1 genes associated with GD in Japanese populations [14]. It could be speculated that DRB1*0301 contributed much less to GD in Asians than in Caucasians.…”

Section: Hla-mentioning

confidence: 99%

“…A growing number of studies suggest that amino acid variation due to variant diversity of HLA alleles is the driving force behind HLA gene conferring susceptibility or protecting properties to GD [14,19,38]. Katahira DRB1*0701 [19].…”

Section: Mechanisms By Which Hla-drb1 Alleles Can Affect To Gdmentioning

confidence: 99%

“…On the other hand, three-dimensional structure of the DR peptide-binding pocket are modified by the amino acids that comprise the DRβ chain, affecting the presentation of peptide antigens to T-cell receptors which cause or prevent the disease from happening [3] has a tendency to increase the risk of GD. However, if the amino acid at position 9 is the uncharged DRb1-Cys9, it is protective against GD [14]. GD-protective DRβ1-Cys9 is encoded by DRB1*0101 and DRB1*1502 alleles.…”

Section: Mechanisms By Which Hla-drb1 Alleles Can Affect To Gdmentioning

confidence: 99%

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Association Between HLA-DRB1 Alleles and Gravesʼ Disease in Asian Populations: A Meta-Analysis

Li,

Ke,

Wang

et al. 2024

Horm Metab Res

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Graves’ disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism. Genetic studies have shown that human leukocyte antigen (HLA) plays an important role in the development of GD. In this article, we performed a meta-analysis determined to evaluate the relationship between HLA-DRB1 alleles and GD. This meta-analysis included 9 studies (3582 cases in the case group and 23070 cases in the control group) and 27 alleles was performed. The combined results showed that, compared with the control group, GD patients have a significant increase in the frequency of DRB1*1403 (OR=2.50, 95% CI=1.78–3.51, pc<0.0001) and have a significant decrease in frequencies of DRB1* 0101 (OR=0.45, 95% CI=0.34–0.59, pc<0.0001) and DRB1*0701 (OR=0.44, 95% CI=0.35–0.55, pc<0.0001). The meta-analysis indicated that, in Asian populations, DRB1*1403 is a risk allele for GD, and DRB1*0101 and DRB1*0701 are protective against the occurrence of GD. We surprisingly discovered that the susceptibility alleles for GD in Asian populations are completely different from Caucasians and the protective alleles for GD in Asians are quite similar to those of Caucasians. The results of our study may provide new opportunities for gene-targeted therapy for GD in Asian populations.

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Section: Introductionmentioning

confidence: 87%

Section: Hla-mentioning

confidence: 99%

Section: Mechanisms By Which Hla-drb1 Alleles Can Affect To Gdmentioning

confidence: 99%

Section: Mechanisms By Which Hla-drb1 Alleles Can Affect To Gdmentioning

confidence: 99%

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Association Between HLA-DRB1 Alleles and Gravesʼ Disease in Asian Populations: A Meta-Analysis

Li,

Ke,

Wang

et al. 2024

Horm Metab Res

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“…This has now been refined such that in populations of European decent, an associated haplotype HLA-DRB1*0301-DQB1*0201-DQA1*0501 has been confirmed in many different studies, with an odds ratio between 2 and 3 compared to the unaffected population [ 19 , 20 ]. In Asian populations, different HLA associations have been confirmed, including DRB1*0405 and DRB1*1403 in Japanese [ 21 , 22 ], DRB1*0803 and DRB1*1602 in Koreans [ 23 ], and DRB1*1602 in the Thai population [ 24 ]. The associated DRB1*0301 allele encodes for an arginine residue at position 74 of the MHC-DRβ chain, and this has been hypothesized to change the binding pocket of the MHC to facilitate binding of T lymphocyte peptide antigen [ 25 ].…”

Section: Historical Genetic Studies: Candidate Gene Studies and The T...mentioning

confidence: 99%

The genetics of Graves’ disease

Grixti,

Lane,

Pearce

2023

Rev Endocr Metab Disord

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Graves’ disease (GD) is the commonest cause of hyperthyroidism and has a strong female preponderance. Everyday clinical practice suggests strong aggregation within families and twin studies demonstrate that genetic factors account for 60-80% of risk of developing GD. In this review, we collate numerous genetic studies and outline the discoveries over the years, starting with historic candidate gene studies and then exploring more recent genome-wide linkage and association studies, which have involved substantial cohorts of East Asian patients as well as those of European descent. Variants in genes including HLA, CTLA4, and PTPN22 have been shown to have substantial individual effects on disease susceptibility. In addition, we examine emerging evidence concerning the possibility that genetic variants may correlate with relevant clinical phenotypes including age of onset of GD, severity of thyrotoxicosis, goitre size and relapse of hyperthyroidism following antithyroid drug therapy, as well as thyroid eye disease. This review supports the inheritance of GD as a complex genetic trait, with a growing number of more than 80 susceptibility loci identified so far. Future implementation of more targeted clinical therapies requires larger studies investigating the influence of these genetic variants on the various phenotypes and different outcomes of conventional treatments.

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