Kendall-Taylor P, Stephenson A, Stratton A, Papiha S S, Perros P, Roberts D F
Department of Medicine, University of Newcastle upon Tyne, UK.
Clin Endocrinol (Oxf). 1988 Jun;28(6):601-10. doi: 10.1111/j.1365-2265.1988.tb03851.x.
Graves' hyperthyroidism and dysthyroid eye disease are closely related autoimmune conditions. Whether the eye disease is an integral part of Graves' disease or a separate entity is controversial. To investigate this we have examined the genetic associations of ophthalmopathy and hyperthyroidism, and compared their phenotype and gene frequencies with a control normal population. HLA-A, B, and DR antigens were typed in 67 patients with dysthyroid eye disease (GO), 60 hyperthyroid patients without significant eye disease (HT) and 500 normal subjects. Patients were also typed for a variety of other genetic markers: blood group systems (10), serum proteins (6) and red cell enzyme systems (10). Increased frequency of B8 and DR3 in Graves' disease was confirmed; B17 occurred less frequently and appears to be protective. HLA antigen frequencies for GO did not differ from HT. The MNS blood group showed a significant association with Graves' disease, the HT patients having a deficit of the s gene compared with controls. The most interesting finding was an increased frequency of blood group P in GO patients compared with either HT or controls. Significant differences were not seen with any of the other HLA antigens, blood groups, protein or enzyme markers considered individually. Multivariate analysis applied first to the HLA and then to the non-HLA systems indicated clear separation of the two patient groups. Although Graves' eye disease shares the same HLA associations as hyperthyroidism, it differs in the increased frequency of P blood group, suggesting that additional genetic factors may determine which patients with Graves' disease develop ophthalmopathy.
格雷夫斯病甲亢和甲状腺功能异常性眼病是密切相关的自身免疫性疾病。眼病是格雷夫斯病的一个组成部分还是一个独立的实体存在争议。为了对此进行研究，我们检测了眼病和甲亢的基因关联性，并将它们的表型和基因频率与正常对照人群进行了比较。对67例甲状腺功能异常性眼病（GO）患者、60例无明显眼病的甲亢患者（HT）和500名正常受试者进行了HLA-A、B和DR抗原分型。还对患者进行了多种其他基因标记物的分型：血型系统（10种）、血清蛋白（6种）和红细胞酶系统（10种）。格雷夫斯病中B8和DR3频率增加得到证实；B17出现频率较低，似乎具有保护作用。GO患者的HLA抗原频率与HT患者无差异。MNS血型与格雷夫斯病存在显著关联，HT患者与对照组相比s基因缺乏。最有趣的发现是，与HT患者或对照组相比，GO患者中血型P的频率增加。对任何其他单独考虑的HLA抗原、血型、蛋白质或酶标记物均未发现显著差异。首先对HLA系统然后对非HLA系统进行多变量分析表明，两组患者有明显区分。虽然格雷夫斯眼病与甲亢有相同的HLA关联，但它在血型P频率增加方面有所不同，这表明可能有其他遗传因素决定哪些格雷夫斯病患者会发生眼病。
