The genetics of Graves' disease.
Autoimmune thyroid disease
Genome-wide association
Genotype-phenotype correlation
Graves’ disease
Immunogenetics
Thyroid eye disease
Journal
Reviews in endocrine & metabolic disorders
ISSN: 1573-2606
Titre abrégé: Rev Endocr Metab Disord
Pays: Germany
ID NLM: 100940588
Informations de publication
Date de publication:
18 Dec 2023
18 Dec 2023
Historique:
accepted:
27
10
2023
medline:
18
12
2023
pubmed:
18
12
2023
entrez:
18
12
2023
Statut:
aheadofprint
Résumé
Graves' disease (GD) is the commonest cause of hyperthyroidism and has a strong female preponderance. Everyday clinical practice suggests strong aggregation within families and twin studies demonstrate that genetic factors account for 60-80% of risk of developing GD. In this review, we collate numerous genetic studies and outline the discoveries over the years, starting with historic candidate gene studies and then exploring more recent genome-wide linkage and association studies, which have involved substantial cohorts of East Asian patients as well as those of European descent. Variants in genes including HLA, CTLA4, and PTPN22 have been shown to have substantial individual effects on disease susceptibility. In addition, we examine emerging evidence concerning the possibility that genetic variants may correlate with relevant clinical phenotypes including age of onset of GD, severity of thyrotoxicosis, goitre size and relapse of hyperthyroidism following antithyroid drug therapy, as well as thyroid eye disease. This review supports the inheritance of GD as a complex genetic trait, with a growing number of more than 80 susceptibility loci identified so far. Future implementation of more targeted clinical therapies requires larger studies investigating the influence of these genetic variants on the various phenotypes and different outcomes of conventional treatments.
Identifiants
pubmed: 38108994
doi: 10.1007/s11154-023-09848-8
pii: 10.1007/s11154-023-09848-8
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/S001611/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V005898/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
Références
Nyström HF, Jansson S, Berg G. Incidence rate and clinical features of hyperthyroidism in a long-term iodine sufficient area of Sweden (Gothenburg) 2003–2005. Clinical Endocrinology. 2013;78(5):768–76.
pubmed: 23421407
doi: 10.1111/cen.12060
Holm IA, Manson JE, Michels KB, Alexander EK, Willett WC, Utiger RD. Smoking and other lifestyle factors and the risk of Graves’ hyperthyroidism. Arch Intern Med. 2005;165(14):1606–11. https://doi.org/10.1001/archinte.165.14.1606 . PMID: 16043678.
doi: 10.1001/archinte.165.14.1606
pubmed: 16043678
Conrad N, Misra S, Verbakel JY, Verbeke G, Molenberghs G, Taylor PN, Mason J, Sattar N, McMurray JJV, McInnes IB, Khunti K, Cambridge G. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet. 2023;S0140–6736(23):00457–9. https://doi.org/10.1016/S0140-6736(23)00457-9 . PMID: 37156255.
doi: 10.1016/S0140-6736(23)00457-9
McLeod DS, Caturegli P, Cooper DS, Matos PG, Hutfless S. Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel. JAMA. 2014;311(15):1563–5. https://doi.org/10.1001/jama.2013.285606 . PMID: 24737370.
doi: 10.1001/jama.2013.285606
pubmed: 24737370
Brix TH, Kyvik KO, Christensen K, Hegedüs L. Evidence for a major role of heredity in Graves’ disease: A population-based study of two Danish twin cohorts. J Clin Endocrinol Metabol. 2001;86(2):930–4.
Skov J, Eriksson D, Kuja-Halkola R, Höijer J, Gudbjörnsdottir S, Svensson AM, Magnusson PKE, Ludvigsson JF, Kämpe O, Bensing S. Co-aggregation and heritability of organ-specific autoimmunity: a population-based twin study. Eur J Endocrinol. 2020;182(5):473–80. https://doi.org/10.1530/EJE-20-0049 . 32229696.
doi: 10.1530/EJE-20-0049
pubmed: 32229696
pmcid: 7182094
Stenszky V, Kozma L, Balázs C, Rochlitz S, Bear JC, Farid NR. The genetics of Graves’ disease: HLA and disease susceptibility. J Clin Endocrinol Metab. 1985;61(4):735–40. https://doi.org/10.1210/jcem-61-4-735 . PMID: 3861611.
doi: 10.1210/jcem-61-4-735
pubmed: 3861611
Vaidya B, Kendall-Taylor P, Pearce SH. The genetics of autoimmune thyroid disease. J Clin Endocrinol Metab. 2002;87(12):5385–97. https://doi.org/10.1210/jc.2002-020492 . PMID: 12466323.
doi: 10.1210/jc.2002-020492
pubmed: 12466323
Vyse TJ, Todd JA. Genetic analysis of autoimmune disease. Cell. 1996;85(3):311–8. https://doi.org/10.1016/s0092-8674(00)81110-1 . PMID: 8616887.
doi: 10.1016/s0092-8674(00)81110-1
pubmed: 8616887
Strieder TGA, Tijssen JGP, Wenzel BE, Endert E, Wiersinga WM. Prediction of progression to overt hypothyroidism or hyperthyroidism in female relatives of patients with autoimmune thyroid disease using the thyroid events Amsterdam (THEA) score. Arch Internal Med. 2008;168(15):1657–63.
doi: 10.1001/archinte.168.15.1657
Song H, Fang F, Tomasson G, Arnberg FK, Mataix-Cols D, Fernández de la Cruz L, Almqvist C, Fall K, Valdimarsdóttir UA. Association of Stress-Related Disorders With Subsequent Autoimmune Disease. JAMA 2018;319(23):2388-2400.
Vestergaard P. Smoking and thyroid disorders–a meta-analysis. Eur J Endocrinol. 2002;146(2):153–61. https://doi.org/10.1530/eje.0.1460153 . PMID: 11834423.
doi: 10.1530/eje.0.1460153
pubmed: 11834423
Bülow Pedersen I, Knudsen N, Jørgensen T, Perrild H, Ovesen L, Laurberg P. Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey. J Clin Endocrinol Metab. 2002;87(10):4462–9. https://doi.org/10.1210/jc.2002-020750 . PMID: 12364419.
doi: 10.1210/jc.2002-020750
pubmed: 12364419
Limbach M, Saare M, Tserel L, Kisand K, Eglit T, Sauer S, et al. Epigenetic profiling in CD4+ and CD8+ T cells from Graves’ disease patients reveals changes in genes associated with T cell receptor signaling. J Autoimmun. 2016;67:46–56.
pubmed: 26459776
doi: 10.1016/j.jaut.2015.09.006
Cai TT, Muhali FS, Song RH, Qin Q, Wang X, Shi LF, et al. Genome-wide DNA methylation analysis in Graves’ disease. Genomics. 2015;105:204–10. https://doi.org/10.1016/j.ygeno.2015.01.001 .
doi: 10.1016/j.ygeno.2015.01.001
pubmed: 25617714
Xin Z, Hua L, Shi TT, Tuo X, Yang FY, Li Y, Cao X, Yang JK. A genome-wide DNA methylation analysis in peripheral blood from patients identifies risk loci associated with Graves' orbitopathy. J Endocrinol Invest 2018;41(6):719-727. https://doi.org/10.1007/s40618-017-0796-6 . PMID: 29190000.
Shi TT, Hua L, Xin Z, Li Y, Liu W, Yang YL. Identifying and Validating Genes with DNA Methylation Data in the Context of Biological Network for Chinese Patients with Graves' Orbitopathy. Int J Endocrinol 2019;2019:6212681. https://doi.org/10.1155/2019/6212681 . PMID: 31001336.
Grumet FC, Payne RO, Kinishi J, Kriss JP. HL A antigens as markers for disease susceptibility and autoimmunity in Grave’s disease. Journal of Clinical Endocrinology and Metabolism. 1974;39(6):1115–9.
pubmed: 4479624
doi: 10.1210/jcem-39-6-1115
Yanagawa T, Mangklabruks A, Chang YB, Okamoto Y, Fisfalen ME, Curran PG, et al. Human histocompatibility leukocyte antigen-DQA1*0501 allele associated with genetic susceptibility to graves’ disease in a caucasian population. Journal of Clinical Endocrinology and Metabolism. 1993;76(6):1569–74.
pubmed: 8501164
Heward JM, Allahabadia A, Daykin J, Carr-Smith J, Daly A, Armitage M, et al. Linkage disequilibrium between the human leukocyte antigen class II region of the major histocompatibility complex and Graves’ disease: Replication using a population case control and family-based study. Journal of Clinical Endocrinology and Metabolism. 1998;83(10):3394–7.
pubmed: 9768636
Katahira M, Ogata H, Takashima H, Ito T, Hodai Y, Miwata T, Goto M, Yamaguchi M, Mizoguchi A, Kawakubo M, Nakamura S. Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves’ disease and Hashimoto’s thyroiditis in the Japanese population. Hum Immunol. 2021;82(4):226–31.
pubmed: 33386169
doi: 10.1016/j.humimm.2020.12.007
Ueda S, Oryoji D, Yamamoto K, Noh JY, Okamura K, Noda M, Kashiwase K, Kosuga Y, Sekiya K, Inoue K, Yamada H, Oyamada A, Nishimura Y, Yoshikai Y, Ito K, Sasazuki T. Identification of independent susceptible and protective HLA alleles in Japanese autoimmune thyroid disease and their epistasis. J Clin Endocrinol Metab. 2014;99(2):E379-83.
pubmed: 24285682
doi: 10.1210/jc.2013-2841
Park MH, Park YJ, Song EY, Park H, Kim TY, Park DJ, Park KS, Cho BY. Association of HLA-DR and -DQ genes with Graves disease in Koreans. Hum Immunol. 2005;66(6):741–7.
pubmed: 15993720
doi: 10.1016/j.humimm.2005.03.001
Wongsurawat T, Nakkuntod J, Charoenwongse P, Snabboon T, Sridama V, Hirankarn N. The association between HLA class II haplotype with Graves’ disease in Thai population. Tissue Antigens. 2006;67(1):79–83.
pubmed: 16451208
doi: 10.1111/j.1399-0039.2005.00498.x
Ban Y, Davies TF, Greenberg DA, Concepcion ES, Osman R, Oashi T, Tomer Y. Arginine at position 74 of the HLA-DR beta1 chain is associated with Graves’ disease. Genes Immun. 2004;5(3):203–8.
pubmed: 15029234
doi: 10.1038/sj.gene.6364059
Yanagawa T, Hidaka Y, Guimaraes V, Soliman M, DeGroot LJ. CTLA-4 gene polymorphism associated with Graves’ disease in a Caucasian population. J Clin Endocrinol Metab. 1995;80(1):41–5.
pubmed: 7829637
Kavvoura FK, Akamizu T, Awata T, Ban Y, Chistiakov DA, Frydecka I, Ghaderi A, Gough SC, Hiromatsu Y, Ploski R, Wang PW, Ban Y, Bednarczuk T, Chistiakova EI, Chojm M, Heward JM, Hiratani H, Juo SH, Karabon L, Katayama S, Kurihara S, Liu RT, Miyake I, Omrani GH, Pawlak E, Taniyama M, Tozaki T, Ioannidis JP. Cytotoxic T-lymphocyte associated antigen 4 gene polymorphisms and autoimmune thyroid disease: a meta-analysis. J Clin Endocrinol Metab. 2007;92(8):3162–70.
pubmed: 17504905
doi: 10.1210/jc.2007-0147
Vaidya B, Imrie H, Perros P, Dickinson J, McCarthy MI, Kendall-Taylor P, Pearce SH. Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers susceptibility to thyroid associated orbitopathy. Lancet. 1999;354(9180):743–4.
pubmed: 10475192
doi: 10.1016/S0140-6736(99)01465-8
Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet. 2004;36(4):337–8.
pubmed: 15004560
doi: 10.1038/ng1323
Velaga MR, Wilson V, Jennings CE, Owen CJ, Herington S, Donaldson PT, Ball SG, James RA, Quinton R, Perros P, Pearce SH. The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves’ disease. J Clin Endocrinol Metab. 2004;89(11):5862–5.
pubmed: 15531553
doi: 10.1210/jc.2004-1108
Smyth D, Cooper JD, Collins JE, Heward JM, Franklyn JA, Howson JM, Vella A, Nutland S, Rance HE, Maier L, Barratt BJ, Guja C, Ionescu-Tîrgoviste C, Savage DA, Dunger DB, Widmer B, Strachan DP, Ring SM, Walker N, Clayton DG, Twells RC, Gough SC, Todd JA. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes. 2004;53(11):3020–3.
pubmed: 15504986
doi: 10.2337/diabetes.53.11.3020
Tomer Y, Barbesino G, Greenberg DA, Concepcion ES, Davies TF. Mapping the major susceptibility loci for familial Graves’ and Hashimoto’s diseases: evidence for genetic heterogeneity and gene interactions. J Clin Endocrinol Metab. 1999;84:4656–64.
pubmed: 10599734
Taylor JC, Gough SC, Hunt PJ, Brix TH, Chatterjee K, Connell JM, Franklyn JA, Hegedus L, Robinson BG, Wiersinga WM, Wass JA, Zabaneh D, Mackay I, Weetman AP. A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease. J Clin Endocrinol Metab. 2006;91(2):646–53. https://doi.org/10.1210/jc.2005-0686 . Epub 2005 Nov 8 PMID: 16278270.
doi: 10.1210/jc.2005-0686
pubmed: 16278270
Vaidya B, Imrie H, Perros P, Young ET, Kelly WF, Carr D, Large DM, Toft AD, McCarthy MI, Kendall-Taylor P, Pearce SH. The cytotoxic T lymphocyte antigen-4 is a major Graves’ disease locus. Hum Mol Genet. 1999;8(7):1195–9. https://doi.org/10.1093/hmg/8.7.1195 . PMID: 10369864.
doi: 10.1093/hmg/8.7.1195
pubmed: 10369864
Tomer Y, Ban Y, Concepcion E, Barbesino G, Villanueva R, Greenberg DA, Davies TF. Common and unique susceptibility loci in Graves and Hashimoto diseases: results of whole-genome screening in a data set of 102 multiplex families. Am J Hum Genet. 2003;73(4):736-47. https://doi.org/10.1086/378588 . Epub 2003 Sep 12. PMID: 12973666; PMCID: PMC1180598.
Dechairo BM, Zabaneh D, Collins J, Brand O, Dawson GJ, Green AP, et al. Association of the TSHR gene with Graves’ disease: The first disease specific locus. European Journal of Human Genetics. 2005;13(11):1223–30.
pubmed: 16106256
doi: 10.1038/sj.ejhg.5201485
Płoski R, Brand OJ, Jurecka-Lubieniecka B, Franaszczyk M, Kula D, Krajewski P, Karamat MA, Simmonds MJ, Franklyn JA, Gough SC, Jarząb B, Bednarczuk T. Thyroid stimulating hormone receptor (TSHR) intron 1 variants are major risk factors for Graves’ disease in three European Caucasian cohorts. PLoS One. 2010;5(11): e15512.
pubmed: 21124799
pmcid: 2991361
doi: 10.1371/journal.pone.0015512
Colobran R, Armengol Mdel P, Faner R, Gärtner M, Tykocinski LO, Lucas A, Ruiz M, Juan M, Kyewski B, Pujol-Borrell R. Association of an SNP with intrathymic transcription of TSHR and Graves’ disease: a role for defective thymic tolerance. Hum Mol Genet. 2011;20(17):3415–23.
pubmed: 21642385
doi: 10.1093/hmg/ddr247
Pujol-Borrell R, Álvarez-Sierra D, Jaraquemada D, Marín-Sánchez A, Colobran R. Central Tolerance Mechanisms to TSHR in Graves’ Disease: Contributions to Understand the Genetic Association. Horm Metab Res. 2018;50(12):863–70.
pubmed: 30396220
doi: 10.1055/a-0755-7927
Wellcome Trust Case Control Consortium; Australo-Anglo-American Spondylitis Consortium (TASC); Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskivina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop TD, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Matthew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop MG, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A; Biologics in RA Genetics and Genomics Study Syndicate (BRAGGS) Steering Committee; Bruce IN, Donovan H, Eyre S, Gilbert PD, Hilder SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S; Breast Cancer Susceptibility Collaboration (UK); Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Newport M, Sirugo G, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Davison D, Ferreira T, Pereira-Gale J, Hallgrimsdo'ttir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Brown MA, Compston A, Farrall M, Hall AS, Hattersley AT, Hill AV, Parkes M, Pembrey M, Stratton MR, Mitchell SL, Newby PR, Brand OJ, Carr-Smith J, Pearce SH, McGinnis R, Keniry A, Deloukas P, Reveille JD, Zhou X, Sims AM, Dowling A, Taylor J, Doan T, Davis JC, Savage L, Ward MM, Learch TL, Weisman MH, Brown M. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007;39(11):1329-37.
Owen CJ, Kelly H, Eden JA, Merriman ME, Pearce SH, Merriman TR. Analysis of the Fc receptor-like-3 (FCRL3) locus in Caucasians with autoimmune disorders suggests a complex pattern of disease association. J Clin Endocrinol Metab. 2007;92(3):1106–11. https://doi.org/10.1210/jc.2006-2183 . Epub 2007 Jan 2 PMID: 17200162.
doi: 10.1210/jc.2006-2183
pubmed: 17200162
Chistiakov DA, Chistiakov AP. Is FCRL3 a new general autoimmunity gene? Hum Immunol. 2007;68(5):375–83. https://doi.org/10.1016/j.humimm.2007.01.013 .
doi: 10.1016/j.humimm.2007.01.013
pubmed: 17462505
Newby PR, Pickles OJ, Mazumdar S, Brand OJ, Carr-Smith JD, Pearce SH, Franklyn JA; Wellcome Trust Case-Control Consortium (WTCCC); Evans DM, Simmonds MJ, Gough SC. Follow-up of potential novel Graves' disease susceptibility loci, identified in the UK WTCCC genome-wide nonsynonymous SNP study. Eur J Hum Genet. 2010 ;18(9):1021-6. https://doi.org/10.1038/ejhg.2010.55 .
Sakai K, Shirasawa S, Ishikawa N, Ito K, Tamai H, Kuma K, Akamizu T, Tanimura M, Furugaki K, Yamamoto K, Sasazuki T. Identification of susceptibility loci for autoimmune thyroid disease to 5q31– q33 and Hashimoto’s thyroiditis to 8q23– q24 by multipoint affected sib-pair linkage analysis in Japanese. Hum Mol Genet. 2001;10:1379–86.
pubmed: 11440990
doi: 10.1093/hmg/10.13.1379
Jin Y, Teng W, Ben S, Xiong X, Zhang J, Xu S, Shugart YY, Jin L, Chen J, Huang W. Genome-wide scan of Graves’ disease: evidence for linkage on chromosome 5q31 in Chinese Han pedigrees. J Clin Endocrinol Metab. 2003;88(4):1798–803. https://doi.org/10.1210/jc.2001-011980 . PMID: 12679476.
doi: 10.1210/jc.2001-011980
pubmed: 12679476
Song HD, Liang J, Shi JY, Zhao SX, Liu Z, Zhao JJ, Peng YD, Gao GQ, Tao J, Pan CM, Shao L, Cheng F, Wang Y, Yuan GY, Xu C, Han B, Huang W, Chu X, Chen Y, Sheng Y, Li RY, Su Q, Gao L, Jia WP, Jin L, Chen MD, Chen SJ, Chen Z, Chen JL. 2009. Functional SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves' disease. Hum Mol Genet. 2009;18(6):1156-70. https://doi.org/10.1093/hmg/ddn442 .
Zhou Z, Zuo CL, Li XS, Ye XP, Zhang QY, Wang P, Zhang RX, Chen G, Yang JL, Chen Y, Ma QY, Song HD. Uterus globulin associated protein 1 (UGRP1) is a potential marker of progression of Graves’ disease into hypothyroidism. Mol Cell Endocrinol. 2019;20(494): 110492. https://doi.org/10.1016/j.mce.2019.110492 .
doi: 10.1016/j.mce.2019.110492
Simmonds MJ, Yesmin K, Newby PR, Brand OJ, Franklyn JA, Gough SC. Confirmation of association of chromosome 5q31-33 with United Kingdom Caucasian Graves’ disease. Thyroid. 2010;20(4):413–7. https://doi.org/10.1089/thy.2009.0375 . PMID: 20210668.
doi: 10.1089/thy.2009.0375
pubmed: 20210668
Chu X, Pan CM, Zhao SX, Liang J, Gao GQ, Zhang XM, Yuan GY, Li CG, Xue LQ, Shen M, Liu W, Xie F, Yang SY, Wang HF, Shi JY, Sun WW, Du WH, Zuo CL, Shi JX, Liu BL, Guo CC, Zhan M, Gu ZH, Zhang XN, Sun F, Wang ZQ, Song ZY, Zou CY, Sun WH, Guo T, Cao HM, Ma JH, Han B, Li P, Jiang H, Huang QH, Liang L, Liu LB, Chen G, Su Q, Peng YD, Zhao JJ, Ning G, Chen Z, Chen JL, Chen SJ, Huang W, Song HD; China Consortium for Genetics of Autoimmune Thyroid Disease. A genome-wide association study identifies two new risk loci for Graves' disease. Nat Genet. 2011;43(9):897-901. https://doi.org/10.1038/ng.898 .
Zhao SX, Xue LQ, Liu W, Gu ZH, Pan CM, Yang SY, Zhan M, Wang HN, Liang J, Gao GQ, Zhang XM, Yuan GY, Li CG, Du WH, Liu BL, Liu LB, Chen G, Su Q, Peng YD, Zhao JJ, Ning G, Huang W, Liang L, Qi L, Chen SJ, Chen Z, Chen JL, Song HD; China Consortium for the Genetics of Autoimmune Thyroid Disease. Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis. Hum Mol Genet. 2013;22(16):3347-62. https://doi.org/10.1093/hmg/ddt183 .
Gu LQ, Zhu W, Zhao SX, Zhao L, Zhang MJ, Cui B, Song HD, Ning G, Zhao YJ. Clinical associations of the genetic variants of CTLA-4, Tg, TSHR, PTPN22, PTPN12 and FCRL3 in patients with Graves’ disease. Clin Endocrinol (Oxf). 2010;72(2):248–55. https://doi.org/10.1111/j.1365-2265.2009.03617.x .
doi: 10.1111/j.1365-2265.2009.03617.x
pubmed: 19438904
Liu W, Wang HN, Gu ZH, Yang SY, Ye XP, Pan CM, Zhao SX, Xue LQ, Xie HJ, Yu SS, Guo CC, Du WH, Liang J, Zhang XM, Yuan GY, Li CG, Su Q, Gao GQ, Song HD; China Consortium for the Genetics of Autoimmune Thyroid Disease. Identification of BACH2 as a susceptibility gene for Graves' disease in the Chinese Han population based on a three-stage genome-wide association study. Hum Genet. 2014;133(5):661-71. https://doi.org/10.1007/s00439-013-1404-2 .
Cooper JD, Simmonds MJ, Walker NM, Burren O, Brand OJ, Guo H, Wallace C, Stevens H, Coleman G; Wellcome Trust Case Control Consortium; Franklyn JA, Todd JA, Gough SC. Seven newly identified loci for autoimmune thyroid disease. Hum Mol Genet. 2012;21(23):5202-8. https://doi.org/10.1093/hmg/dds357 .
Muto A, Tashiro S, Nakajima O, Hoshino H, Takahashi S, Sakoda E, Ikebe D, Yamamoto M, Igarashi K. The transcriptional programme of antibody class switching involves the repressor Bach2. Nature. 2004;429(6991):566–71. https://doi.org/10.1038/nature02596 .
doi: 10.1038/nature02596
pubmed: 15152264
Pazderska A, Oftedal BE, Napier CM, Ainsworth HF, Husebye ES, Cordell HJ, Pearce SH, Mitchell AL. A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison’s Disease in Humans. J Clin Endocrinol Metab. 2016;101(11):3865–9. https://doi.org/10.1210/jc.2016-2368 .
doi: 10.1210/jc.2016-2368
pubmed: 27680876
pmcid: 5095240
McAllister K, Yarwood A, Bowes J, Orozco G, Viatte S, Diogo D, Hocking LJ, Steer S, Wordsworth P, Wilson AG, Morgan AW. UK Rheumatoid Arthritis Genetics Consortium; Rheumatoid Arthritis Consortium International; Identification of BACH2 and RAD51B as rheumatoid arthritis susceptibility loci in a meta-analysis of genome-wide data. Arthritis Rheum. 2013;65(12):3058–62. https://doi.org/10.1002/art.38183 .
doi: 10.1002/art.38183
pubmed: 24022229
pmcid: 4034583
Cooper JD, Smyth DJ, Smiles AM, Plagnol V, Walker NM, Allen JE, Downes K, Barrett JC, Healy BC, Mychaleckyj JC, Warram JH, Todd JA. Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nat Genet. 2008;40(12):1399-401. https://doi.org/10.1038/ng.249 . Epub 2008 Nov 2. PMID: 18978792; PMCID: PMC2635556.
Saevarsdottir S, Olafsdottir TA, Ivarsdottir EV, et al. FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease. Nature. 2020;584:619–23. https://doi.org/10.1038/s41586-020-2436-0 .
doi: 10.1038/s41586-020-2436-0
pubmed: 32581359
Wang K, Zhu Q, Lu Y, Lu H, Zhang F, Wang X, Fan Y. CTLA-4 +49 G/A Polymorphism Confers Autoimmune Disease Risk: An Updated Meta-Analysis. Genet Test Mol Biomarkers. 2017;21(4):222–7.
pubmed: 28384040
doi: 10.1089/gtmb.2016.0335
Eliana F, Suwondo P, Asmarinah A, et al. The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) Gene, Thyroid Stimulating Hormone Receptor (TSHR) Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease. Acta Med Indones. 2017;49(3):195–204.
pubmed: 29093229
Tanrikulu S, Erbil Y, Ademoglu E, et al. The predictive value of CTLA-4 and Tg polymorphisms in the recurrence of Graves’ disease after antithyroid withdrawal. Endocrine. 2006;30(3):377–81.
pubmed: 17526951
doi: 10.1007/s12020-006-0017-0
Sahin M, Erdogan MF, Erdogan G. Cytotoxic T lymphocyte-associated molecule-4 polymorphisms in Turkish Graves’ disease patients and association with probability of remission after antithyroid therapy. Eur J Intern Med. 2005;16(5):352–5.
pubmed: 16137550
doi: 10.1016/j.ejim.2005.06.007
Vos XG, Wiersinga WM, Endert E, Zwinderman AH, Tijssen JGP. Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves’ Hyperthyroidism. The Journal of Clinical Endocrinology & Metabolism. 2016;101(4):1381–9.
doi: 10.1210/jc.2015-3644
Kuś A, Radziszewski M, Glina A, Szymański K, Jurecka-Lubieniecka B, Pawlak-Adamska E, Kula D, Wawrusiewicz-Kurylonek N, Kuś J, Miśkiewicz P, Płoski R, Bolanowski M, Daroszewski J, Jarząb B, Bossowski A, Bednarczuk T. Paediatric-onset and adult-onset Graves’ disease share multiple genetic risk factors. Clin Endocrinol (Oxf). 2019;90(2):320–7.
pubmed: 30358895
doi: 10.1111/cen.13887
Lane LC, Kuś A, Bednarczuk T, Bossowski A, Daroszewski J, Jurecka-Lubieniecka B, Cordell HJ, Pearce SHS, Cheetham T, Mitchell AL. An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts. J Clin Endocrinol Metab. 2020;105(9):e3277-84.
pubmed: 32501499
pmcid: 7382372
doi: 10.1210/clinem/dgaa347
García-Mayor RV, Álvarez-Vázquez P, Fluiters E, Valverde D, Andrade A. Long-term remission following antithyroid drug withdrawal in patients with Graves’ hyperthyroidism: parameters with prognostic value. Endocrine. 2019;63(2):316–22.
pubmed: 30334140
doi: 10.1007/s12020-018-1785-z
Hsiao JY, Hsieh MC, Tien KJ, Hsu SC, Shin SJ, Lin SR. Association between a C/T polymorphism in exon 33 of the thyroglobulin gene is associated with relapse of Graves’ hyperthyroidism after antithyroid withdrawal in Taiwanese. J Clin Endocrinol Metab. 2007;92(8):3197–201.
pubmed: 17550957
doi: 10.1210/jc.2007-0675
Wang PW, Chen IY, Liu RT, Hsieh CJ, Hsi E, Juo SH. CTLA-4 gene polymorphism and hyperthyroid Graves’ disease relapse after antithyroid drug withdrawal: a follow-up study. J Clin Endocrinol Metab. 2007;92:2513–8.
pubmed: 17426089
doi: 10.1210/jc.2006-2761
Wang PW, Chen IY, Juo SH, Hsi E, Liu RT, Hsieh CJ. Genotype and phenotype predictors of relapse of graves’ disease after antithyroid drug withdrawal. Eur Thyroid J. 2013;1(4):251–8.
pubmed: 24783027
doi: 10.1159/000342621
Vejrazkova D, Vcelak J, Vaclavikova E, Vankova M, Zajickova K, Vrbikova J, Duskova M, Pacesova P, Novak Z, Bendlova B. Recurrence of Graves’ Disease: What Genetics of HLA and PTPN22 Can Tell Us. Front Endocrinol (Lausanne). 2021;23(12): 761077.
doi: 10.3389/fendo.2021.761077
Kinjo Y, Takasu N, Komiya I, et al. Remission of Graves’ hyperthyroidism and A/G polymorphism at position 49 in exon 1 of cytotoxic T lymphocyte-associated molecule-4 gene. J Clin Endocrinol Metab. 2002;87(6):2593–6.
pubmed: 12050220
Kim KW, Park YJ, Kim TY, Park DJ, Park KS, Cho BY. Susceptible alleles of the CD40 and CTLA-4 genes are not associated with the relapse after antithyroid withdrawal in Graves’ disease. Thyroid. 2007;17(12):1229–34.
pubmed: 17949264
doi: 10.1089/thy.2007.0011
Vejrazkova D, Vcelak J, Vaclavikova E, Vankova M, Zajickova K, Vrbikova J, Duskova M, Pacesova P, Novak Z, Bendlova B. Recurrence of Graves’ Disease: What Genetics of HLA and PTPN22 Can Tell Us. Front Endocrinol (Lausanne). 2021;23(12): 761077.
doi: 10.3389/fendo.2021.761077
Allison JP, Krummel MF. The Yin and Yang of T cell costimulation. Science. 1995;270(5238):932–3.
pubmed: 7481795
doi: 10.1126/science.270.5238.932
Vang T, Liu WH, Delacroix L, Wu S, Vasile S, Dahl R, Yang L, Musumeci L, Francis D, Landskron J, Tasken K, Tremblay ML, Lie BA, Page R, Mustelin T, Rahmouni S, Rickert RC, Tautz L. LYP inhibits T-cell activation when dissociated from CSK. Nat Chem Biol. 2012;8(5):437–46.
pubmed: 22426112
pmcid: 3329573
doi: 10.1038/nchembio.916
Ban Y, Davies TF, Greenberg DA, Kissin A, Marder B, Murphy B, Concepcion ES, Villanueva RB, Barbesino G, Ling V, Tomer Y. Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease. Genes Immun. 2003;4(8):586–93.
pubmed: 14647199
doi: 10.1038/sj.gene.6364018
Valta M, Gazali AM, Viisanen T, et al. Type 1 diabetes linked PTPN22 gene polymorphism is associated with the frequency of circulating regulatory T cells. Eur J Immunol. 2020;50(4):581–8.
pubmed: 31808541
doi: 10.1002/eji.201948378
Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009;229(1):152–72.
pubmed: 19426221
doi: 10.1111/j.1600-065X.2009.00782.x
Faustino LC, Kahaly GJ, Frommer L, Concepcion E, Stefan-Lifshitz M, Tomer Y. Precision Medicine in Graves’ Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody. Front Endocrinol (Lausanne). 2021;4(12): 691781.
doi: 10.3389/fendo.2021.691781
Li CW, Osman R, Menconi F, Concepcion E, Tomer Y. Cepharanthine blocks TSH receptor peptide presentation by HLA-DR3: Therapeutic implications to Graves’ disease. J Autoimmun. 2020;108: 102402.
pubmed: 31980336
pmcid: 7819272
doi: 10.1016/j.jaut.2020.102402
Gong ST, Chao IM. Changes in serum thyroglobulin and thyroid autoantibodies in patients with Graves’ disease treated with antithyroid drug and their relationship to relapse. J Formos Med Assoc. 1991;90(12):1155–62.
pubmed: 1724781
Simmonds MJ, Howson JM, Heward JM, et al. Regression mapping of association between the human leukocyte antigen region and Graves disease. Am J Hum Genet. 2005;76(1):157–63.
pubmed: 15558498
doi: 10.1086/426947
Chen PL, Shih SR, Wang PW, Lin YC, Chu CC, Lin JH, Chen SC, Chang CC, Huang TS, Tsai KS, Tseng FY, Wang CY, Lu JY, Chiu WY, Chang CC, Chen YH, Chen YT, Fann CS, Yang WS, Chang TC. Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat Commun. 2015;7(6):7633.
doi: 10.1038/ncomms8633