Philippou G, Krimitzas A, Kaltsas G, Anastasiou E, Souvatzoglou A, Alevizaki M
1st Endocrine Section, Athens University School of Medicine, Alexandra Hospital, Greece.
J Endocrinol Invest. 2001 Feb;24(2):88-91. doi: 10.1007/BF03343819.
Genes of, or closely associated to, the HLA complex are assumed to contribute to the genetic predisposition of Graves' disease. The aim of this study was to investigate the presence of the HLA DQA10501 and DRB10301 antigens in Greek patients with Graves' disease. In addition, we tried to establish if there is any association between these antigens and any of the clinical manifestations of the disease. We examined 117 patients with Graves' disease and 104 healthy controls. DNA was extracted from peripheral lymphocytes and the HLA DQA10501 and DRB10301 genomic regions were amplified by PCR and characterized by hybridization with sequence specific oligonucleotides (SSO). Two of the patients had a positive family history for Graves' disease and 46 had clinical thyroid eye disease (TED). The frequencies of both DQA10501 and DRB10301 antigens were significantly increased in patients compared to controls (relative risk [RR] 4.2 and 4.5 for each antigen respectively). Neither of these two antigens was an independent risk factor for Graves' disease. However, the combination of both these HLA antigens resulted in a striking increase in the RR for development of Graves' disease especially in females (RR/F=27, RR/M=8.4). No association was found between these antigens and positive family history or the presence of TED. These data suggest that HLA DQA10501 and DRB10301 antigens are not independent risk factors for the development of Graves' disease. On the contrary, the presence of both these alleles results in a significant increase in the RR for the development of Graves' disease in the Greek population, particularly in females.
与HLA复合体相关或紧密相连的基因被认为与格雷夫斯病的遗传易感性有关。本研究的目的是调查希腊格雷夫斯病患者中HLA DQA10501和DRB10301抗原的存在情况。此外，我们试图确定这些抗原与该疾病的任何临床表现之间是否存在关联。我们检查了117例格雷夫斯病患者和104名健康对照者。从外周淋巴细胞中提取DNA，通过聚合酶链反应（PCR）扩增HLA DQA10501和DRB10301基因组区域，并通过与序列特异性寡核苷酸（SSO）杂交进行鉴定。其中两名患者有格雷夫斯病的阳性家族史，46例有临床甲状腺眼病（TED）。与对照组相比，患者中DQA10501和DRB10301抗原的频率均显著增加（每种抗原的相对风险[RR]分别为4.2和4.5）。这两种抗原都不是格雷夫斯病的独立危险因素。然而，这两种HLA抗原的组合导致格雷夫斯病发病的RR显著增加，尤其是在女性中（RR/F = 27，RR/M = 8.4）。未发现这些抗原与阳性家族史或TED的存在之间存在关联。这些数据表明，HLA DQA10501和DRB10301抗原不是格雷夫斯病发病的独立危险因素。相反，在希腊人群中，尤其是女性中，这两种等位基因的存在导致格雷夫斯病发病的RR显著增加。
