HLA-DPB1*0202 Is Associated with a Predictor of Good Prognosis of Graves’ Disease in the Japanese

Takahashi, Megumi; Yasunami, Michio; Kubota, Sumihisa; Tamai, Hiroshi; Kimura, Akinori

doi:10.1016/j.humimm.2006.02.023

Cited by 24 publications

(19 citation statements)

References 35 publications

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“…The TBII-negative patients were randomly selected from the previously reported 97 patients, 9 whereas the TBII-positive patients were those analyzed previously 8 (n¼142) and newly recruited patients (n¼98). The diagnosis of GD and assay for TBII were performed as described previously.…”

Section: Materials and Methods Subjectsmentioning

confidence: 99%

“…9 The CTLA4 polymorphism (CT60, rs3087243) was analyzed by the PCR-restriction-fragment length polymorphism method using HpyCh4IV. 10,16 …”

Section: Genotypingmentioning

confidence: 99%

“…8 In addition, we demonstrated that HLA-A*02 and DPB1*0202 showed association with TBII-negative GD, indicating that the TBII-negative GD was different in HLA-linked genetic factors from the TBII-positive GD. 9 There are several other genetic factors associated with GD, including polymorphisms in the gene for cytotoxic T-lymphocyte-associated antigen-4 (CTLA4). 10 CTLA4 encodes a co-stimulatory molecule of T cells, which is involved in the regulation of T-cell activation, 11,12 and it has been reported that the polymorphisms in exon 1 and 3¢-UTR region are associated with GD as well as Hashimoto thyroiditis, another autoimmune thyroid disease, in European and Asian populations.…”

Section: Introductionmentioning

confidence: 99%

“…The diagnosis of GD and assay for TBII were performed as described previously. 2,3,9 Blood sample to prepare genomic DNA was obtained from each subject under a given informed consent. …”

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confidence: 99%

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HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves’ disease

Takahashi

Kimura

2010

J Hum Genet

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Graves' disease (GD) is an autoimmune disease characterized by hyperthyroidism due to the presence of autoantibodies against thyroid-stimulating hormone receptor, which is measured as thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII). Most of the GD patients are TBII-positive, but TBII is undetectable in a proportion of GD patients. We previously reported the association of HLA-A*02 and -DPB1*0501 with TBII-positive GD, whereas TBII-negative GD showed association with HLA-A*02 and DPB1*0202. Recently, polymorphisms of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) gene are reported to be associated with GD. In this study, we investigated 329 (240 TBII-positive and 89 TBII-negative) GD patients and 378 controls for the polymorphisms in HLA-A, -DPB1 and CTLA4 (CT60, rs3087243, A/G) to investigate the contribution of these factors in the susceptibility to GD. A significant association with CTLA4 was found for the TBII-positive GD (G carriers in patients vs controls, 97.1 vs 91.8%; odds ratio (OR)¼2.97, 95% confidence interval¼1.29-6.87, P¼0.008), but the association was weak and not significant for the TBII-negative GD (94.4 vs 91.8%; OR¼1.50, 95% confidence interval¼0.57-3.98, P¼0.41). Stratification analyses suggested a possible synergistic interaction of CTLA4 with HLA-A*02 and -DPB1*0501 in the susceptibility to TBII-positive GD. INTRODUCTIONGraves' disease (GD) is a typical organ-specific autoimmune disease affecting thyroid gland, in which autoantibodies against the receptors for thyroid-stimulating hormone induce hyperthyroidism. The autoantibodies has been measured as thyroid-stimulating antibodies (TSAb) by a biological assay or as thyroid-stimulating hormonebinding inhibitory immunoglobulins (TBII) by a solid phase assay. 1 Although most of the GD patients are positive for both TBII and TSAb, a proportion of the patients carry low or undetectable level of TBII (TBII-negative GD). 2 However, TSAb can be detected in the TBII-negative GD, and it was reported that the TBII-negative patients exhibited mild goiter and followed benign prognosis, implying that the TBII-negative GD might be a clinical subtype different from the ordinary TBII-positive GD. 3 Etiological mechanisms of GD are not fully understood, but certain genetic factors should be involved in the pathogenesis because of familial aggregation of the disease. 4 To decipher the genetic factors candidate gene approaches have been used, and it is well documented that human leukocyte antigen (HLA) polymorphisms are associated with GD, such that HLA-B*08-DRB1*03-DQA1*05-DQB1*02 haplotype showed strong association in European populations. 5,6 However, the distribution of HLA alleles and haplotypes are quite different in different ethnic groups, and the European GD-associated HLA haplotype is virtually absent in Japanese. 7 We previously reported that HLA-A*02 and DPB1*0501 are associated with Japanese GD. 8 In addition, we demonstrated that HLA-A*02 and DPB1*0202 showed association with TBII-negative GD, indicating that the T...

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Section: Materials and Methods Subjectsmentioning

confidence: 99%

“…9 The CTLA4 polymorphism (CT60, rs3087243) was analyzed by the PCR-restriction-fragment length polymorphism method using HpyCh4IV. 10,16 …”

Section: Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The diagnosis of GD and assay for TBII were performed as described previously. 2,3,9 Blood sample to prepare genomic DNA was obtained from each subject under a given informed consent. …”

mentioning

confidence: 99%

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HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves’ disease

Takahashi

Kimura

2010

J Hum Genet

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“…Using 361 multiethnic samples including African (YRI), European (CEU), Chinese (CHB) and Japanese (JPT) samples, de Bakker et al 2 produced a high-resolution HLA and SNP haplotype map in the extended human MHC region (26)(27)(28)(29)(30)(31)(32)(33)(34) Mb of chromosome 6). The study elucidated detailed LD structures in this region and provided information about the correlation between HLA alleles and SNPs.…”

Section: Introductionmentioning

confidence: 99%

HLA and SNP haplotype mapping in the Japanese population

2012

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The genes that encode the human leukocyte antigen (HLA) class I and II molecules are highly polymorphic and located in the major histocompatibility complex (MHC) region, where there is a high density of immune-related genes. Numerous studies have identified disease susceptibility in this region; however, interpretation of the results is complicated because of the strong linkage disequilibrium (LD) among HLA alleles and single-nucleotide polymorphisms (SNPs). In this study, we evaluated the correlation between the HLA alleles of 6 loci (HLA-A, C, B, DRB1, DQB1 and DPB1) and 6502 SNPs within 8 Mb of the extended MHC region using 92 Japanese subjects to identify SNP single loci or haplotypes that tag HLA alleles. We found a total of 39 HLA alleles that showed strong LD (r 2 X0.8) with SNPs, including 11 non-synonymous SNPs in non-HLA genes. In addition, we identified several SNP haplotypes in strong LD (r 2 X0.8) with eight HLA alleles, which do not possess tag SNPs. Our detailed list of tag SNPs and haplotypes could be utilized for a better understanding of the results obtained by association studies in the Japanese population and for the characterization of the differences in LD structures between races.

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Neoself Antigens Presented on MHC Class II Molecules in Autoimmune Diseases

Jin,

Arase

2024

Advances in Experimental Medicine and Biology

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HLA-DPB1*0202 Is Associated with a Predictor of Good Prognosis of Graves’ Disease in the Japanese

Cited by 24 publications

References 35 publications

HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves’ disease

HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves’ disease

HLA and SNP haplotype mapping in the Japanese population

Neoself Antigens Presented on MHC Class II Molecules in Autoimmune Diseases

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