Tomer Y, Davies T F
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Baillieres Clin Endocrinol Metab. 1997 Oct;11(3):431-50. doi: 10.1016/s0950-351x(97)80678-7.
Graves' disease (GD) develops as a result of a complex interaction between genetic susceptibility genes and likely environmental factors. Most epidemiological data support an important genetic contribution to the development of GD. The concordance rate of GD in monozygotic twins is 30-60% and in dizygotic twins 3-9%, and thyroid autoantibodies have been reported in up to 50% of the siblings of patients with GD. For many years now, HLA studies have consistently shown an increased frequency of HLA-DR3 in Caucasian patients with GD; but with only a risk ratio of 3-5. However, recent advances in human genome mapping techniques have enabled the study of many other candidate genes. Of these additional, non-HLA genes, only CTLA-4 has been consistently found to be associated with GD. Using a linkage based approach which only detects highly significant susceptibility genes we have recently reported preliminary results which demonstrated that a marker located approximately 25 cM from the TSH receptor gene on chromosome 14q31 is linked to GD and in the same vicinity as the IDDM-11 locus. Such results, if confirmed, may signal the presence of a gene family related to endocrine autoimmunity on chromosome 14q31.
格雷夫斯病（GD）是由遗传易感基因与可能的环境因素之间复杂的相互作用所导致的。大多数流行病学数据支持遗传因素在GD发病中起重要作用。单卵双胞胎中GD的一致率为30 - 60%，双卵双胞胎中为3 - 9%，并且据报道，GD患者的兄弟姐妹中高达50%存在甲状腺自身抗体。多年来，HLA研究一直表明，白种人GD患者中HLA - DR3的频率增加；但风险比仅为3 - 5。然而，人类基因组图谱技术的最新进展使得能够研究许多其他候选基因。在这些额外的非HLA基因中，仅发现细胞毒性T淋巴细胞相关抗原4（CTLA - 4）一直与GD相关。使用一种仅检测高度显著易感基因的连锁分析方法，我们最近报告了初步结果，该结果表明位于14号染色体q31上距促甲状腺激素受体基因约25厘摩（cM）处的一个标记与GD连锁，且与1型糖尿病11位点（IDDM - 11 locus）在同一区域。如果这些结果得到证实，可能表明在14号染色体q31上存在一个与内分泌自身免疫相关的基因家族。
