Horm Metab Res 2009; 41(6): 430-435
DOI: 10.1055/s-0029-1220902
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

The T393C Polymorphism of the Gαs Gene (GNAS1) is Associated with the Course of Graves' Disease

D. Glowacka 1 , C. Loesch 2 , K. T. M. Johnson 1 , K. Mann 3 , J. Esser 1 , N. G. Morgenthaler 4 , W. Siffert 5 , K. W. Schmid 6 , A. K. Eckstein 1
  • 1Department of Ophthalmology, University Hospital of Essen, University of Duisburg-Essen, Germany
  • 2Institute of Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University of Duisburg-Essen, Germany
  • 3Department of Medicine, University Hospital of Essen, Division of Endocrinology, University of Duisburg-Essen, Germany
  • 4Institut für Experimentelle Endokrinologie und Endokrinologisches Forschungszentrum EnForCé, Charité, Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
  • 5Institute of Pharmacogenetics, University Hospital of Essen, University of Duisburg-Essen, Germany
  • 6Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Germany
Further Information

Publication History

received 13.02.2009

accepted 20.04.2009

Publication Date:
09 June 2009 (online)


Genotypes of the T393C SNP of GNAS1, a gene that encodes for the Gαs subunit of G proteins have been significantly associated with the clinical course in a variety of cancers. Since this SNP may also influence the course of Graves’ disease (GD) and, especially, Graves’ ophthalmopathy (GO), we determined genotype and allele frequency in a series of 359 patients, which were referred to our clinic within 6 months of the onset of GO. Among them, 336 patients also suffered from associated hyperthyroidism. Data on relapse and remission rates 12 months after termination of a 1 year antithyroid drug therapy was available for 276 patients. As controls, 820 healthy individuals were recruited. Our data suggest that the T393C SNP does not represent a risk factor for the development of both GD and GO. It was, however, significantly associated with the course of hyperthyroidism (p=0.013) and a similar trend was evident for the course of GO (p=0.093). Homozygous TT carriers showed a significantly increased risk (p=0.03) for hyperthyroidism to relapse (OR 2.4; 95% CI 1.1–5.4). Also, the TT genotype was associated with significantly increased serum TRAb levels (CC+CT: 5.4 IU/l vs. TT: 9.3 IU/l). This is probably caused by increased G-Protein susceptibility to TSHR-mediated stimulation through TRAb. Genotyping of the T393C SNP of GNAS1 may become a useful additional tool to predict the clinical course of GD and GO. This may allow the clinician to identify patients at risk for more severe courses of disease and to come to more timely decisions for treatment.



A. K. Eckstein, MD 

Department of Ophthalmology

University Hospital of Essen

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45122 Essen


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Email: [email protected]