HUMAN HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN-DQA1-ASTERISK-0501 ALLELE ASSOCIATED WITH GENETIC SUSCEPTIBILITY TO GRAVES-DISEASE IN A CAUCASIAN POPULATION
HUMAN HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN-DQA1-ASTERISK-0501 ALLELE ASSOCIATED WITH GENETIC SUSCEPTIBILITY TO GRAVES-DISEASE IN A CAUCASIAN POPULATION
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DOI：
10.1210/jcem.76.6.8501164
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发表时间：
1993-06-01
影响因子：
5.8
通讯作者：
DEGROOT, LJ
中科院分区：
文献类型：
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作者：
YANAGAWA, T;MANGKLABRUKS, A;DEGROOT, LJ
Graves病（GD）是一种甲状腺自身免疫性疾病。假设HLA复合体的基因或与HLA复合体密切相关的基因有助于GD的遗传易感性。我们以前曾报道过在白种人GD患者中HLA-DR 3/DQ 2的频率增加，最近DRB 3基因编码的Dw 24的重要性已被提出。为了进一步研究GD与这些基因的相关性，采用序列特异性寡核苷酸探针分析聚合酶链反应扩增DNA（PCR-SSO），对94例无关GD患者和75例对照受试者进行HLA-DRB 3、-DRB 1、-DQA 1和-DQB 1分型。这些研究得出了三个结果。1)DQA 1 *0501阳性受试者的频率在患者中显著增加（GD，73.4% vs.对照组42.7%，P = 0.0001，Pc < 0.001，RR = 3.71）。与DQA 1 *0501紧密连锁不平衡的DR 3（GD，34.0% vs.对照组17.3%，P = 0.0146，RR = 2.46）的频率也增加;然而，当P值针对检测的抗原数量进行校正时，其不显著。DQB 1和DRB 3等位基因频率均未显著增加。2)排除DR 3阳性受试者后，患者中DQA 1 *0501仍显著增加（GD，59.7% vs.对照组30.6%，P = 0.0012，Pc < 0.01，RR = 3.35）。3)Dw 24和Dw 25，26（Dw 25或Dw 26）在DR 3阳性组和阴性组中的分布均无显著性差异，提示DQA 1 *0501或一个与之密切相关的未知基因与GD的易感性有关，而Dw 24与GD的易感性无关。然而，由于与DQA 1 *0501的固定联系，DR 3的重要性仍有待阐明。
Graves' disease (GD) is an autoimmune disease of the thyroid gland. Genes of, or closely associated to, the HLA complex are assumed to contribute to the genetic predisposition to GD. We have previously reported an increased frequency of HLA-DR3/DQ2 in Caucasian patients with GD, and recently the importance of Dw24 encoded by DRB3 gene has been suggested. To further investigate the associations of GD and these genes, 94 unrelated patients with GD and 75 control subjects were typed for HLA-DRB3, -DRB1, -DQA1, and -DQB1, using sequence-specific oligonucleotide probes to analyze polymerase chain reaction amplified DNA (PCR-SSO). Three findings emerged from these studies. 1) The frequency of subjects positive for DQA1*0501 (GD, 73.4% vs. control 42.7%, P = 0.0001, Pc < 0.001, RR = 3.71) was significantly increased among patients. The frequency of DR3 (GD, 34.0% vs. control 17.3%, P = 0.0146, RR = 2.46), which is in tight linkage disequilibrium with DQA1*0501, was also increased; however, it was not significant when the P value was corrected for the number of antigens tested. Neither DQB1 nor DRB3 alleles were significantly increased in frequency. 2) After exclusion of DR3-positive subjects, DQA1*0501 was still significantly increased (GD, 59.7% vs. control 30.6%, P = 0.0012, Pc < 0.01, RR = 3.35) among patients. 3) The distributions of Dw24 and Dw25,26 (Dw25 or Dw26) did not differ between patients and controls on either DR3 positive or negative groups.These findings suggest that DQA1*0501, or a closely associated unknown gene, confers susceptibility to GD, while Dw24 is not directly involved. The importance of DR3, however, remains to be elucidated, because of the fixed linkage with DQA1*0501.