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Intercellular Adhesion Molecule 1 Gene Polymorphisms in Graves’ Disease

Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok (A.K., N.W., K.M., J.M., I.K.); and Department of Computer Science, Technical University of Bialystok (M.K.), 15-267 Bialystok, Poland

Address all correspondence and requests for reprints to: Dr. Adam Kretowski, Department of Endocrinology, Diabetology, and Internal Medicine, Medical Academy of Bialystok, M. Sklodowska-Curie 24 a, 15-267 Bialystok, Poland. E-mail: akretows{at}amb.ac.bialystok.pl.

It was recently suggested that genetic factors could play a major role in the development of Graves’ disease (GD). The aim of the present study was to evaluate the frequency of the c.721GA polymorphism and the c.1405AG polymorphism of the intercellular adhesion molecule 1 (ICAM-1) gene in subjects with GD compared with that in healthy controls, because ICAM-1 was found to play a key role in lymphocyte infiltration into the thyroid gland and the concentration of the soluble form of ICAM-1 correlates significantly with the clinical activity and treatment status in GD. We have analyzed the association of ICAM-1 polymorphisms with the age at onset of GD and the presence of ophthalmopathy. In a group of 235 patients with GD and 211 healthy controls we have shown that polymorphism at position c.721GA is associated with an earlier age of GD onset and that the c.1405AG polymorphism of the ICAM-1 gene could predispose to Graves’ ophthalmopathy. This suggests that G241R and K469E amino acid substitutions in the ICAM-1 molecule could influence the intensity/duration of the autoimmunity process and the infiltration of orbital tissues. It could be speculated that therapy that modulates ICAM-1 function may delay the onset and/or prolong the remission and/or have an influence on clinical manifestations of GD.

Abbreviations: GD, Graves’ disease; GO, Graves’ ophtalmopathy; ICAM-1, intercellular adhesion molecule 1; LFA-1, leukocyte function-associated antigen 1; P_c, corrected P; sICAM-1, soluble form of ICAM-1; TSHR Ab, TSH receptor antibodies.

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