Chen Q Y, Nadell D, Zhang X Y, Kukreja A, Huang Y J, Wise J, Svec F, Richards R, Friday K E, Vargas A, Gomez R, Chalew S, Lan M S, Tomer Y, Maclaren N K
The Research Institute for Children, Children's Hospital, Harahan, Louisiana 70123, USA.
J Clin Endocrinol Metab. 2000 Apr;85(4):1545-9. doi: 10.1210/jcem.85.4.6523.
Information on genetic susceptibility to Graves' disease in African Americans is limited. We studied DRB1, DQB1, DRB3 subtypes, DQA10501, DQA10201, and CTLA-4 polymorphisms in 49 African American patients with adult onset Graves' disease and 47 racially-matched controls using PCR-based sequence-specific priming methods. There were no significant differences in DRB1 or DQB1 allelic frequencies or CTLA-4 polymorphisms between patients and controls. However, we found that the frequency of DRB3 was significantly increased in the patients (75.5% vs. 57.4%, P = 0.006, X2 = 3.52), especially for the DRB30202 subtype (53.1% vs. 23.4, P = 0.003, X2 = 8.91). In this one respect, the finding was in concordance with our previous observations in Caucasian patients with adult-onset Graves' disease. In addition, whereas the frequency of DQA10501 was increased (P = 0.018, X2 = 5.63) in our patients, the haplotype of DRB3/DQA10501, or DRB30202/DQA10501 was found to be more strongly associated (P = 0.008, X2 = 7.0; P = 0.0008, X2 = 11.34, respectively). These data suggest that DRB30202, particularly when found with DQA1*0501 in a haplotype is a susceptible gene(s) for Graves' disease in adult African Americans. Considering these data with those in Caucasian patients, our results would suggest that the primary Graves susceptible locus is likely DRB3 and not DRB1.
非裔美国人中格雷夫斯病遗传易感性的信息有限。我们使用基于聚合酶链反应的序列特异性引物方法，研究了49例成年起病的非裔美国格雷夫斯病患者和47例种族匹配的对照者的DRB1、DQB1、DRB3亚型、DQA10501、DQA10201和细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因多态性。患者与对照者之间的DRB1或DQB1等位基因频率或CTLA-4基因多态性无显著差异。然而，我们发现患者中DRB3的频率显著增加（75.5%对57.4%，P = 0.006，X2 = 3.52），尤其是DRB30202亚型（53.1%对23.4%，P = 0.003，X2 = 8.91）。在这一方面，该发现与我们之前对成年起病的白种人格雷夫斯病患者的观察结果一致。此外，虽然我们的患者中DQA10501的频率增加（P = 0.018，X2 = 5.63），但发现DRB3/DQA10501或DRB30202/DQA10501单倍型的关联性更强（分别为P = 0.008，X2 = 7.0；P = 0.0008，X2 = 11.34）。这些数据表明，DRB30202，特别是当与DQA1*0501存在于一个单倍型中时，是成年非裔美国人格雷夫斯病的易感基因。结合白种人患者的数据来看，我们的结果表明格雷夫斯病的主要易感基因座可能是DRB3而非DRB1。
