HLA - DRB1*08、DRB1*03/DRB3*0101和DRB3*0202是北美白种人Graves病的易感基因，而DRB1*07具有保护作用。
HLA-DRB1*08, DRB1*03/DRB3*0101, and DRB3*0202 are susceptibility genes for Graves' disease in North American Caucasians, whereas DRB1*07 is protective.
作者信息
Chen Q Y, Huang W, She J X, Baxter F, Volpe R, Maclaren N K
机构信息
The Research Institute for Children, Harahan, Louisiana 70123, USA.
出版信息
J Clin Endocrinol Metab. 1999 Sep;84(9):3182-6. doi: 10.1210/jcem.84.9.5991.
Graves' disease is known to be HLA-D associated; however, the primary loci involved remain unclear. We examined HLA genotypes of DRB1 and DQB1 plus DRB3 subtypes using PCR-based sequence-specific priming in two groups of North American (Gainesville, FL; and Toronto, Canada) Caucasian patients with Graves' disease. We stratified patients into those with either early age at onset (<20 yr; 13.1 +/- 4.8 yr; n = 30) and later age at onset of disease (38.8 +/- 9.7 yr; n = 62) and compared the results to 192 normal controls. As expected, we found that DRB103 was associated with Graves' disease, but at a higher odds ratios for early-onset than later-onset patients (3.7 vs. 2.2). The frequency of DRB108 was also increased in both groups of patients, but significantly so only in patients with early-onset Graves' (P = 0.001; chi2 = 10.8). DRB3 was highly associated with Graves' in both groups of patients (P = 0.009; chi2 = 6.83 and P = 0.0015; chi2 = 10.1, respectively); however, the subtypes of DRB3 revealed differential susceptibilities. Whereas the frequencies of both DRB30101 and DRB30202 were increased over the entire cohort, that of DRB30301 was not. Significant P values were found for DRB30101 in patients with early-onset and for DRB30202 in patients with later onset of Graves' disease. When the haplotypes of DRB103-DRB3 of all subtypes were removed for analysis (all DRB103 positive also had DRB30101), the frequency of DRB30202 remained significantly higher in the patients with later onset of Graves' disease than in controls (P = 0.0043; chi2 = 8.13), but DRB3 was no longer positively associated with the early-onset group. In addition, we found that DRB107 was negatively associated with both groups of patients (P = 0.024; chi2 = 5.10 and P = 0.0085; chi2 = 6.93). These data suggest that DRB30202 is more likely to be the primary susceptible locus than DRB103 for patients with later onset of Graves' disease.
已知格雷夫斯病与HLA - D相关；然而，所涉及的主要基因座仍不清楚。我们使用基于聚合酶链反应的序列特异性引物，对两组北美（佛罗里达州盖恩斯维尔市；以及加拿大多伦多市）患有格雷夫斯病的白种人患者的DRB1、DQB1以及DRB3亚型的HLA基因型进行了检测。我们将患者分为发病年龄早（<20岁；13.1±4.8岁；n = 30）和发病年龄晚（38.8±9.7岁；n = 62）两组，并将结果与192名正常对照进行比较。正如预期的那样，我们发现DRB103与格雷夫斯病相关，但发病早的患者的优势比高于发病晚的患者（3.7对2.2）。两组患者中DRB108的频率也有所增加，但仅在发病早的格雷夫斯病患者中显著增加（P = 0.001；卡方值 = 10.8）。DRB3在两组患者中均与格雷夫斯病高度相关（分别为P = 0.009；卡方值 = 6.83和P = 0.0015；卡方值 = 10.1）；然而，DRB3的亚型显示出不同的易感性。虽然DRB30101和DRB30202在整个队列中的频率均增加，但DRB30301并非如此。在发病早的患者中，DRB30101有显著的P值，在发病晚的格雷夫斯病患者中，DRB30202有显著的P值。当去除所有亚型的DRB103 - DRB3单倍型进行分析时（所有DRB103阳性的患者也有DRB30101），发病晚的格雷夫斯病患者中DRB30202的频率仍显著高于对照组（P = 0.0043；卡方值 = 8.13），但DRB3与发病早的组不再呈正相关。此外，我们发现DRB107与两组患者均呈负相关（分别为P = 0.024；卡方值 = 5.10和P = 0.0085；卡方值 = 6.93）。这些数据表明对于发病晚的格雷夫斯病患者，DRB30202比DRB103更有可能是主要的易感基因座。
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