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.
Highlights
IntroductionHepatitis C Virus (HCV) infection is a potentially (persistent normalization of alanine-aminotransferase) life-threatening disease as 75% of affected patients with and virological (sustained negativity for Hepatitis C acute infection develop chronic disease with a high risk Virus [HCV] RNA) response and leads to eradication of of cirrhosis and hepatocellular carcinoma (Carella et al, the virus in less than 60% of patients (Missiha et al., 2004)
Hepatitis C Virus (HCV) infection is a potentially life-threatening disease as 75% of affected patients with and virological response and leads to eradication of of cirrhosis and hepatocellular carcinoma (Carella et al, the virus in less than 60% of patients (Missiha et al., 2004)
The AG genotype was significantly associated with developing either hypothyroidism (Table 2) or grave’s disease (Table 3)
Summary
Hepatitis C Virus (HCV) infection is a potentially (persistent normalization of alanine-aminotransferase) life-threatening disease as 75% of affected patients with and virological (sustained negativity for Hepatitis C acute infection develop chronic disease with a high risk Virus [HCV] RNA) response and leads to eradication of of cirrhosis and hepatocellular carcinoma (Carella et al, the virus in less than 60% of patients (Missiha et al., 2004). Abo El-Khair et al / American Journal of Biochemistry and Biotechnology 8 (3) (2012) 179-194 include systemic and organ-specific pathological changes, many of them being the consequences of immune enhancement or immune dysregulation induced by IFN itself (Carella et al, 2004). The main effect of IFN-α on the immune system is the enhancement of cell cytotoxicity, which is important for antineoplastic and antiviral activity (Carella et al, 2004). The widespread effects of IFN α on the immune system may be important for inducing thyroid disease because peripheral features of systemic immune involvement have been described in patients with thyroid autoimmunity (Ciampolillo et al, 2003). The critical point is to understand how a generalized activation of the immune system, induced by the cytokine treatment, may result in an organ-specific involvement of the thyroid gland (Carella et al, 2004). CTLA-4 is an immune regulatory molecule expressed on the surface of activated T lymphocytes and a key inhibitor of T cell activation (Kavvoura et al, 2007)
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