{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:20:55Z","timestamp":1792686055191,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Approximately half of patients diagnosed with Graves\u2019 disease (GD) relapse within two years of thyreostatic drug withdrawal. It is then necessary to decide whether to reintroduce conservative treatment that can have serious side effects, or to choose a radical approach. Familial forms of GD indicate a significant genetic component. Our aim was to evaluate the practical benefits of HLA and <jats:italic>PTPN22<\/jats:italic> genetic testing for the assessment of disease recurrence risk in the Czech population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 206 patients with GD, exon 2 in the HLA genes <jats:italic>DRB1<\/jats:italic>, <jats:italic>DQA1<\/jats:italic>, <jats:italic>DQB1<\/jats:italic> and rs2476601 in the gene <jats:italic>PTPN22<\/jats:italic> were sequenced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The risk HLA haplotype <jats:italic>DRB1<\/jats:italic>*03-<jats:italic>DQA1<\/jats:italic>*05-<jats:italic>DQB1<\/jats:italic>*02 was more frequent in our GD patients than in the general European population. During long-term retrospective follow-up (many-year to lifelong perspective), 87 patients relapsed and 26 achieved remission lasting over 2 years indicating a 23% success rate for conservative treatment of the disease. In 93 people, the success of conservative treatment could not be evaluated (thyroidectomy immediately after the first attack or ongoing antithyroid therapy). Of the examined genes, the HLA-<jats:italic>DQA1<\/jats:italic>*05 variant reached statistical significance in terms of the ability to predict relapse (p=0.03). Combinations with either both other HLA risk genes forming the risk haplotype <jats:italic>DRB1<\/jats:italic>*03-<jats:italic>DQA1<\/jats:italic>*05-<jats:italic>DQB1<\/jats:italic>*02 or with the <jats:italic>PTPN22<\/jats:italic> SNP did not improve the predictive value.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>the <jats:italic>DQA1<\/jats:italic>*05 variant may be a useful prognostic marker in patients with an unclear choice of treatment strategy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.761077","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T14:31:51Z","timestamp":1638282711000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Recurrence of Graves\u2019 Disease: What Genetics of HLA and PTPN22 Can Tell Us"],"prefix":"10.3389","volume":"12","author":[{"given":"Daniela","family":"Vejrazkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Vcelak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliska","family":"Vaclavikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marketa","family":"Vankova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Zajickova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Vrbikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Duskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Pacesova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenek","family":"Novak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Bendlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0229","article-title":"2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis","volume":"26","author":"Ross","year":"2016","journal-title":"Thyroid"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1159\/000490384","article-title":"2018 European Thyroid Association Guideline for the Management of Graves\u2019 Hyperthyroidism","volume":"7","author":"Kahaly","year":"2018","journal-title":"Eur Thyroid J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.2.7242","article-title":"Evidence for a Major Role of Heredity in Graves\u2019 Disease: A Population-Based Study of Two Danish Twin Cohorts","volume":"86","author":"Brix","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s0889-8529(05)70130-4","article-title":"The Genetics of Graves\u2019 Disease","volume":"29","author":"Gough","year":"2000","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3644","article-title":"Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves\u2019 Hyperthyroidism","volume":"101","author":"Vos","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2011.12.009","article-title":"Involvement of Stress in the Pathogenesis of Autoimmune Thyroid Disease: A Prospective Study","volume":"37","author":"Effraimidis","year":"2012","journal-title":"Psychoneuroendocrinology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-014-0289-8","article-title":"Stress Triggers the Onset and the Recurrences of Hyperthyroidism in Patients With Graves\u2019 Disease","volume":"48","author":"Vita","year":"2015","journal-title":"Endocrine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0539","article-title":"Mechanisms in Endocrinology. 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