Gene analysis of HLA class II antigens in relation to the development of IDDM in Japanese

HLA II 类抗原与日本 IDDM 发生相关的基因分析

基本信息

  • 批准号:
    02454511
  • 负责人:
  • 金额:
    $ 4.22万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
  • 财政年份:
    1990
  • 资助国家:
    日本
  • 起止时间:
    1990 至 1991
  • 项目状态:
    已结题

项目摘要

Insulin-dependent diabetes mellitus (IDDM) occurs as a result of destruction of pancreatic beta cells presumably by autoimmune process. It is related to certain HLA antigens, but the HLA types which correlate with IDDM vary among different ethnic groups. In Caucasians, the presence of Asp at HLA DQ B57 protects from IDDM, but many IDDM patients in Japan have Asp at this position. In order to clarify the IDDM susceptibility HLA antigens in Japanese, we analyzed DRB1, DQA1 and DQB1 genes of IDDM patients by polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that, (1) DR4 and DR9 were positively cor-related while DR2 and DRw11 negatively correlated with IDDM; (2) DR4-Dw15(DRB1*0405), DR9, DQA1*0301, DQB1*0401 alleles were positively correlated with IDDM. As haplotypes, DRB1*0405-DQA1*0301-DQB1*0401(RR=4.4), DRw8-DQA1*0301-DQB1*0302(RR=9.7), and DR9-DQA1*0301-DQB1*0303(RR=2.2) were positively correlated with IDDM. The most susceptible genotype was [DRB1*0405-DQA1*0301-DQB1*0401] / [DRw8-DQA1*0301-DQB1*0302] (RR=18.2); (3) Among 3 families in which a parent and achild had IDDM. DRB1*0405-DQA1*0301-DQB1*0401 was shared in 2 parent-child pairs and DR2-DQA1*0103-DQB1*0601 was shared in one pair. Among 4 IDDM sib pairs, 3 shared two haplotypes, two sharing DRB1*0405-DQA1*0301-DQB1*0401 (homozygotic), and one sharing [DRB1*0403-DQA1*0301-DQB1*0302] / [DRB1*0405-DQA1*0301-DQB1*0401]. One IDDM sib pair shared only one haplotype, DRB1*0405-DQA1*0301-DQB1*0302; (4) Comparison of clinical features and HLA subtypes revealed that DR9, DQA1*0301 and DQB1*0303 were more frequent in CPR-negative patients, and DRB1*0405, DRw8, and DQA1*0401 were more frequent in CPR-positive patients. Patients with thyorid autoantibodies had DR9, DQB1*0303 more often and DRB1*0405, DRw13 and DQA1*0102 less frequently. These data indicate that DRB1, DQA1 and DQB1 genes confer IDDM susceptibility in Japanese and modify clinical features.
胰岛素依赖型糖尿病 (IDDM) 的发生可能是由于自身免疫过程破坏胰腺 β 细胞所致。它与某些HLA抗原有关,但与IDDM相关的HLA类型在不同种族之间有所不同。在白种人中,HLA DQ B57 处存在天冬氨酸可以预防 IDDM,但日本的许多 IDDM 患者在该位置都有天冬氨酸。为了明确日本人IDDM易感性HLA抗原,我们通过聚合酶链反应和序列特异性寡核苷酸杂交分析了IDDM患者的DRB1、DQA1和DQB1基因。我们发现,(1)DR4和DR9与IDDM呈正相关,而DR2和DRw11与IDDM呈负相关; (2)DR4-Dw15(DRB1*0405)、DR9、DQA1*0301、DQB1*0401等位基因与IDDM呈正相关。作为单倍型,DRB1*0405-DQA1*0301-DQB1*0401(RR=4.4)、DRw8-DQA1*0301-DQB1*0302(RR=9.7)和DR9-DQA1*0301-DQB1*0303(RR=2.2)与IDDM呈正相关。最易受影响的基因型是[DRB1*0405-DQA1*0301-DQB1*0401] / [DRw8-DQA1*0301-DQB1*0302](RR=18.2); (3) 3个家庭中,父母和孩子均患有IDDM。 DRB1*0405-DQA1*0301-DQB1*0401 在 2 个父子对中共享,DR2-DQA1*0103-DQB1*0601 在一对中共享。在 4 个 IDDM 同胞对中,3 个共享两个单倍型,两个共享 DRB1*0405-DQA1*0301-DQB1*0401(纯合),一个共享 [DRB1*0403-DQA1*0301-DQB1*0302]/ [DRB1*0405-DQA1*0301-DQB1*0401]。一对 IDDM 同胞仅共享一个单倍型,DRB1*0405-DQA1*0301-DQB1*0302; (4)比较临床特征和HLA亚型发现,DR9、DQA1*0301和DQB1*0303在CPR阴性患者中更常见,DRB1*0405、DRw8和DQA1*0401在CPR阳性患者中更常见。患有甲状腺自身抗体的患者 DR9、DQB1*0303 的发生率较高,DRB1*0405、DRw13 和 DQA1*0102 的发生率较低。这些数据表明 DRB1、DQA1 和 DQB1 基因赋予日本人 IDDM 易感性并改变临床特征。

项目成果

期刊论文数量(45)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
粟田 卓也: "日本人IDDMにおけるHLA-DQβ抗原遺伝子の解析" 分子糖尿病学. 1. 13-17 (1990)
Takuy​​a Awata:“日本 IDDM 中 HLA-DQβ 抗原基因的分析”《分子糖尿病学》1. 13-17 (1990)。
  • DOI:
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    0
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粟田 卓也: "日本人インスリン依存性糖尿病(IDDM)のHLA geme analysis." 糖尿病学1991. 52-65 (1991)
Takuy​​a Awata:“日本胰岛素依赖性糖尿病 (IDDM) 的 HLA 基因分析。糖尿病学 1991. 52-65 (1991)”
  • DOI:
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    0
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葛谷 健: "インスリン依存性糖尿病の成因" 日本臨牀. 48(増). 187-195 (1990)
Ken Kuzutani:“胰岛素依赖性糖尿病的原因”Nippon Rinsho 48(in)。
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    0
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Awata, T. and Kuzuya, T.: "Analysis of HLA DQbeta genes of Japanese IDDM patients (in Japanese)" Molecular Diabetology. 1. 13-17 (1990)
Awata, T. 和 Kuzuya, T.:“日本 IDDM 患者的 HLA DQbeta 基因分析(日语)”分子糖尿病学。
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    0
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  • 通讯作者:
Awata,T.: "Genetic analysis of HLA class II alleles and susceptibility to Type 1(insulin-dependent)diabetes mellitus in Japanese subjects." Diabetologia. 35. 419-424 (1992)
Awata,T.:“日本受试者 HLA II 类等位基因的遗传分析和 1 型(胰岛素依赖型)糖尿病的易感性。”
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    0
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KUZUYA Takeshi其他文献

KUZUYA Takeshi的其他文献

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{{ truncateString('KUZUYA Takeshi', 18)}}的其他基金

Studies on the pathogenesis of diabetes mellitus, with special reference to the abnormality of insulin secretion.
研究糖尿病发病机制,特别是胰岛素分泌异常。
  • 批准号:
    60480276
  • 财政年份:
    1985
  • 资助金额:
    $ 4.22万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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