甲状腺球蛋白基因启动子中的单核苷酸多态性1623 A/G（rs180195）与自身免疫性甲状腺疾病相关，但与甲状腺眼病无关。
Single nucleotide polymorphism 1623 A/G (rs180195) in the promoter of the Thyroglobulin gene is associated with autoimmune thyroid disease but not with thyroid ophthalmopathy.
作者信息
Lahooti Hooshang, Edirimanne Senarath, Walsh John P, Delbridge Leigh, Hibbert Emily J, Wall Jack R
机构信息
Thyroid Research Laboratory, Sydney Medical School - Nepean Clinical School, The University of Sydney, Kingswood, NSW, Australia.
Nepean Blue Mountains Local Health District, Kingswood, NSW, Australia.
出版信息
Clin Ophthalmol. 2017 Jul 25;11:1337-1345. doi: 10.2147/OPTH.S136070. eCollection 2017.
BACKGROUND
Our studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves' ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored.
METHODS
We identified novel variant 1623 A/G single nucleotide polymorphism (SNP) (rs180195) in the promoter of gene associated with autoimmune thyroid disorders. We genotyped the SNPs rs2069566, rs2076739, rs121912646, rs121912647, rs121912648, rs121912649, rs121912650, rs137854433, rs137854434, and rs180195 by MassARRAY SNP analysis using iPLEX technology in a cohort of 529 patients with thyroid autoimmunity with and without ophthalmopathy, and controls.
RESULTS
We showed that variant 1623 A/G SNP (rs180195) in the promoter of gene is a marker for thyroid autoimmunity, but not for ophthalmopathy. We showed that there was a significant difference in the distribution of the major allele (G) vs minor allele (A) in patients with Hashimoto's thyroiditis (HT). In HT the wild-type (GG) genotype was less common. We showed that the genotypes homozygous AA and heterozygous GA rs180195 SNP in the promoter of gene were more closely associated with thyroid autoimmunity than the wild-type (GG) polymorphism, and are thus, markers of autoimmunity.
CONCLUSION
rs180195 SNP was previously identified by Stefan et al independently of us, who showed that this SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between SNPs and HT. Our findings support the notion that the thyroid and orbital disorders are not part of the same disease, ie, "Graves' disease" or "Hashimoto's disease", but separate autoimmune disorders.
背景
近年来我们的研究聚焦于一些关于格雷夫斯眼病特征性眼眶反应发病机制的新观点，即甲状腺组织和眼眶组织表达的抗原会成为自身抗体和/或致敏T细胞的作用靶点，从而导致眼眶炎症。虽然针对促甲状腺激素受体已进行了充分研究，但另一种主要甲状腺抗原甲状腺球蛋白（TG）的可能作用在很大程度上被忽视了。
方法
我们在与自身免疫性甲状腺疾病相关的基因启动子中鉴定出新型1623 A/G单核苷酸多态性（SNP）（rs180195）。我们采用iPLEX技术，通过MassARRAY SNP分析对529例患有或未患有眼病的甲状腺自身免疫患者及对照组的rs2069566、rs2076739、rs121912646、rs121912647、rs121912648、rs121912649、rs121912650、rs137854433、rs137854434和rs180195这些SNP进行基因分型。
结果
我们发现该基因启动子中的1623 A/G SNP（rs180195）是甲状腺自身免疫性的一个标志物，但不是眼病的标志物。我们发现，在桥本甲状腺炎（HT）患者中，主要等位基因（G）与次要等位基因（A）的分布存在显著差异。在HT中，野生型（GG）基因型较少见。我们发现，该基因启动子中rs180195 SNP的纯合子AA和杂合子GA基因型比野生型（GG）多态性与甲状腺自身免疫性的关联更紧密，因此是自身免疫性的标志物。
结论
rs180195 SNP先前由斯特凡等人独立于我们鉴定出来，他们表明该SNP易患自身免疫性甲状腺疾病。然而，这是第一项探索该SNP与HT之间关联的研究。我们的研究结果支持这样一种观点，即甲状腺疾病和眼眶疾病并非同一疾病（即“格雷夫斯病”或“桥本氏病”）的一部分，而是单独的自身免疫性疾病。
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