Intercellular Adhesion Molecule 1 Gene Polymorphisms in Graves’ Disease

• Published in: The journal of clinical endocrinology and metabolism Vol. 88; no. 10; pp. 4945 - 4949
• Main Authors: Kretowski, Adam, Wawrusiewicz, Natalia, Mironczuk, Katarzyna, Mysliwiec, Janusz, Kretowska, Malgorzata, Kinalska, Ida
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.10.2003; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adolescent; Adult; Age of Onset; Aged; Amino acids; Autoimmunity; Biological and medical sciences; Cell adhesion; Child; Endocrinopathies; Female; Gene Frequency; Gene polymorphism; Genetic factors; Genetic Predisposition to Disease; Genotype; Graves disease; Graves Disease - genetics; Humans; Infiltration; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - analysis; Intercellular Adhesion Molecule-1 - genetics; Lymphocytes; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oculomotor Muscles - chemistry; Polymorphism; Polymorphism, Genetic; Remission; Severity of Illness Index; Thyroid. Thyroid axis (diseases); Endocrinopathy; Human; Immunopathology; Intercellular adhesion molecule 1; Hyperthyroidism; Thyroid diseases; Autoimmune disease; Orbit(eye) disease; Genetic determinism; Eye disease; Age of onset; Exophthalmus; Graves disease; Polymorphism
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-030131

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.721G→A polymorphism and the c.1405A→G 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.721G→A is associated with an earlier age of GD onset and that the c.1405A→G 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.