CTLA-4 Gene Polymorphism in Relation to Thyroid Disorders in Patients with Chronic Hepatitis C Under Interferon Alpha Therapy

Abstract

Thyroid autoimmunity and dysfunction have reported as side effects of interferon-α treatment. The CT60 and exon 1+49 A/G polymorphisms in the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene have linked to susceptibility to autoimmune disease. The aim of this research was to analyze the frequencies of CTLA-4 CT60 and +49 A/G polymorphisms and evaluate both polymorphisms as indicators of thyroid disorder susceptibility in chronic HCV Egyptian patients under interferon therapy. This study was carried out on 114 chronic HCV patients under combined therapy of interferon-α and Ribavirin. From them, 60 chronic HCV patients without thyroid disorder were considered the control group. The other 54 patients were having thyroid disorder either hypothyroidism (N = 35) or Grave’s Disease (GD) (N = 19). For all subjects, the genotypes of CTLA-4 gene CT60 and +49 A/G polymorphisms were studied using RFLP technique. For +49 A/G polymorphism, the genotypes frequencies in controls were: AA (30), AG (31.7) and GG (38.3%). Whereas, in hypothyroidism patients, the AA, AG and GG genotypes frequencies were (20), (57.1%) and (22.9%) respectively, while in grave’s disease, the AA, AG and GG genotypes frequencies were (26.3 (57.9) and (15.8%) respectively. The AG genotype was significantly associated with thyroid disease. As regards CT60 polymorphism, the genotypes frequencies in controls were: CC (38.3), CT (35) and TT (26.7%). Whereas, in hypothyroidism patients, the CC, CT and TT genotypes frequencies were (60), (20) and (20%) respectively, while in grave’s disease, the CC, CT and TT genotypes frequencies were (68.4), (15.8) and (15.8%) respectively. The CC genotype was significantly associated with thyroid disorders. CTLA-4 gene +49A/G and CT60 polymorphisms confer susceptibility to autoimmune thyroid disorder and confirm usefulness of CTLA-4 genotyping in predicting thyroid disorder in chronic HCV patients under interferon therapy.