Association of autoimmune thyroid disease with microsatellite markers for the thyrotropin receptor gene and CTLA-4 in Japanese patients
Association of autoimmune thyroid disease with microsatellite markers for the thyrotropin receptor gene and CTLA-4 in Japanese patients
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DOI：
10.1089/thy.2000.10.851
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发表时间：
2000-10-01
期刊：
影响因子：
6.6
通讯作者：
Bowden, DW
中科院分区：
文献类型：
--
作者：
Akamizu, T;Sale, MM;Bowden, DW
在以前的研究中，我们确定了一个微卫星标记附近的促甲状腺激素受体（TSHR）基因。使用该标记物TSHR-CA的研究显示，日本患者的自身免疫性甲状腺疾病（AITD）与微卫星序列的一个特定等位基因（等位基因1; 180个碱基对[bp]）之间存在显著关联。此外，观察到AITD与CTLA-4基因的两个等位基因相关的弱证据。在本研究中，TSHR-CA已被映射到约600 kb的TSHR基因使用辐射杂交作图。对349例日本AITD患者和218例日本对照者进行了TSHR-CA和另一个TSHR微卫星标记TSHR-AT的基因分型。TSHR-AT标记显示在该日本AITD人群中与等位基因5显著增加（294 bp; p < 0.05）和等位基因7显著减少（298 bp; p < 0.05）相关。在甲状腺功能减退患者中，TSHR-AT等位基因5的相关性也是显著的（甲状腺激素结合抑制性免疫球蛋白阳性[TBII+]，P < 0.01;促甲状腺激素结合抑制性免疫球蛋白阴性[TBII-]，P < 0.05）。TSHR-AT等位基因7与甲状腺功能减退症TBII+患者的相关性也显著（p < 0.05）。CTLA-4基因也在日本AITD患者和对照组中进行了基因分型。等位基因2（102 bp; p < 0.01）和等位基因4（106 bp; p < 0.01）与AITD易感性相关。在GD患者中也观察到了这些相关性（等位基因2，p
In a previous study we identified a microsatellite marker near the thyrotropin receptor (TSHR) gene. Studies with this marker, TSHR-CA, revealed a significant association between autoimmune thyroid disease (AITD) in Japanese patients and one specific allele (allele 1; 180 base pair [bp]) of the microsatellite sequence. In addition, weak evidence for association of AITD with two alleles of the CTLA-4 gene was observed. In the present study, TSHR-CA has been mapped to approximately 600 kb of the TSHR gene using radiation hybrid mapping. TSHR-CA and another TSHR microsatellite marker, TSHR-AT, which is located in intron 2 of TSHR gene, were genotyped in a set of 349 unrelated Japanese AITD patients and 218 Japanese controls. The TSHR-AT marker showed association in this Japanese AITD population with a significant increase in allele 5 (294 bp; p < 0.05) and a significant decrease in allele 7 (298 bp; p < 0.05). The association of allele 5 of TSHR-AT was also significant in hypothyroid patients (thyrotopin-binding inhibitory immunoglobulin-positive [TBII+], P < 0.01; thyrotropin binding inhibitory immunoglobulin-negative [TBII-], p < 0.05). The association of allele 7 of TSHR-AT were also significant for the hypothyroid TBII+ patients (p < 0.05). The CTLA-4 gene was also genotyped in this expanded set of Japanese AITD patients and controls. Association between AITD susceptibility and allele 2 (102 bp; p < 0.01) and allele 4 (106 bp; p < 0.01) were observed. These associations were also observed with GD patients (allele 2, p