Genetic profiling in Graves' disease: further evidence for lack of a distinct genetic contribution to Graves' ophthalmopathy.
Genetic profiling in Graves' disease: further evidence for lack of a distinct genetic contribution to Graves' ophthalmopathy.
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DOI：
10.1089/thy.2012.0007
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Xiaoming Yin;R. Latif;R. Bahn;T. Davies
中科院分区：
文献类型：
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作者：
Xiaoming Yin;R. Latif;R. Bahn;T. Davies
背景Graves病（GD），包括Graves眼病或眼眶病（GO），是一种自身免疫性疾病，其病因具有环境和遗传成分。GO临床表型的遗传贡献仍不清楚。来自我们实验室和其他人的先前数据表明，GO没有与GD本身不同的特定遗传成分，而其他报告偶尔出现，表明CTLA 4和IL 23 R等基因的多态性特别增加了GO的风险。对所有这些报告的批评之一是GO表型的临床定义与甲状腺功能亢进GD不同，没有临床意义的眼睛受累。本研究的目的是利用一组表型纯的GD GO患者，并检查一系列与GD相关的基因，以确定是否有任何基因与GO而不是Graves甲状腺疾病本身更明确相关。方法为了进一步研究特定的易感基因是否与GO相关，我们对高度特征化的GO患者进行了进一步的遗传关联研究，其中许多患者因眼球突出而接受了眼眶减压手术。我们对256例严重GO（n=199）和不太严重GO（n=57）的白人患者以及90例GD但无临床明显GO的患者进行了HLA、CTLA 4、IL 23 R和TSHR基因分型。结果：我们发现GO和非GO患者的等位基因和基因型频率在任何评估的基因和基因组合中均无统计学差异。结论：这些结果提供了进一步的证据，GO患者没有明显的遗传易感性，他们的眼睛疾病，并再次表明，环境和/或表观遗传的影响在发挥作用。
BACKGROUND Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy (GO), is an autoimmune disease with an environmental and genetic component to its etiology. The genetic contribution to the GO clinical phenotype remains unclear. Previous data from our laboratory and others have suggested that GO has no specific genetic component distinct from GD itself, while other reports have occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and IL23R specifically increase the risk for GO. One of the criticisms of all these reports has been the clinical definition of the GO phenotype as distinct from hyperthyroid GD devoid of clinically significant eye involvement. The objective of this study was to take advantage of a phenotypically pure group of GD patients with GO and examine a series of genes associated with GD to determine if any were more definitively associated with GO rather than Graves' thyroid disease itself. METHODS To further examine whether specific susceptibility genes are associated with GO, we have performed further genetic association studies using highly characterized GO patients, many of whom had undergone orbital decompression surgery for their exophthalmos. We genotyped HLA, CTLA4, IL23R, and TSHR genes in a group of 256 Caucasian patients with severe GO (n=199) and less severe GO (n=57), and 90 patients with GD but no clinically apparent GO. RESULTS We found that the allele and genotype frequencies were not statistically different between GO and non-GO patients for any of the genes and gene combinations assessed. CONCLUSIONS These results provide further evidence that patients with GO do not have a distinct genetic susceptibility to their eye disease and again suggest that environmental and/or epigenetic influences are at play.