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

Hooshang Lahooti,1,2 Senarath Edirimanne,1,2 John P Walsh,3,4 Leigh Delbridge,5,6 Emily J Hibbert,1,2 Jack R Wall1,2 1Thyroid Research Laboratory, Sydney Medical School – Nepean Clinical School, The University of Sydney, Kingswood, NSW, Australia; 2Nepean Blue Mountains Local Health Distr...

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Autores principales:	Lahooti H, Edirimanne S, Walsh JP, Delbridge L, Hibbert EJ, Wall JR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Thyroglobulin gene Hashimoto's thyroiditis Graves' disease ophthalmopathy autoimmunity Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/99f207d18ff346e1a68733d09dad9eb2
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spelling	oai:doaj.org-article:99f207d18ff346e1a68733d09dad9eb22021-12-02T02:14:45ZSingle nucleotide polymorphism 1623 A/G (rs180195) in the promoter of the Thyroglobulin gene is associated with autoimmune thyroid disease but not with thyroid ophthalmopathy1177-5483https://doaj.org/article/99f207d18ff346e1a68733d09dad9eb22017-07-01T00:00:00Zhttps://www.dovepress.com/single-nucleotide-polymorphism-1623-ag-rs180195-in-the-promoter-of-the-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Hooshang Lahooti,1,2 Senarath Edirimanne,1,2 John P Walsh,3,4 Leigh Delbridge,5,6 Emily J Hibbert,1,2 Jack R Wall1,2 1Thyroid Research Laboratory, Sydney Medical School – Nepean Clinical School, The University of Sydney, Kingswood, NSW, Australia; 2Nepean Blue Mountains Local Health District, Kingswood, NSW, Australia; 3Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; 4School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA, Australia; 5Department of Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia; 6Sydney Medical School – Northern Clinical School, The University of Sydney, NSW, Australia 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 TG gene associated with autoimmune thyroid disorders. We genotyped the TG 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 TG 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 TG 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 TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG 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. Keywords: hyperthyroid, Hashimoto’s, thyroid eye disease, orbital, homozygote, heterozygote, T-cellsLahooti HEdirimanne SWalsh JPDelbridge LHibbert EJWall JRDove Medical PressarticleThyroglobulin geneHashimoto's thyroiditisGraves' diseaseophthalmopathyautoimmunityOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 11, Pp 1337-1345 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Thyroglobulin gene Hashimoto's thyroiditis Graves' disease ophthalmopathy autoimmunity Ophthalmology RE1-994
spellingShingle	Thyroglobulin gene Hashimoto's thyroiditis Graves' disease ophthalmopathy autoimmunity Ophthalmology RE1-994 Lahooti H Edirimanne S Walsh JP Delbridge L Hibbert EJ Wall JR 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
description	Hooshang Lahooti,1,2 Senarath Edirimanne,1,2 John P Walsh,3,4 Leigh Delbridge,5,6 Emily J Hibbert,1,2 Jack R Wall1,2 1Thyroid Research Laboratory, Sydney Medical School – Nepean Clinical School, The University of Sydney, Kingswood, NSW, Australia; 2Nepean Blue Mountains Local Health District, Kingswood, NSW, Australia; 3Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; 4School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA, Australia; 5Department of Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia; 6Sydney Medical School – Northern Clinical School, The University of Sydney, NSW, Australia 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 TG gene associated with autoimmune thyroid disorders. We genotyped the TG 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 TG 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 TG 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 TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG 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. Keywords: hyperthyroid, Hashimoto’s, thyroid eye disease, orbital, homozygote, heterozygote, T-cells
format	article
author	Lahooti H Edirimanne S Walsh JP Delbridge L Hibbert EJ Wall JR
author_facet	Lahooti H Edirimanne S Walsh JP Delbridge L Hibbert EJ Wall JR
author_sort	Lahooti H
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/99f207d18ff346e1a68733d09dad9eb2
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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

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