Association between genetic mutations and the development of autoimmune thyroiditis in patients with chronic hepatitis C treated with interferon alpha

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Considerable progress was made by the introduction of interferon to the treatment of chronic hepatitis C virus infection. This treatment, however, is associated with the risk of developing or exacerbating autoimmune diseases, with chronic autoimmune thyroiditis being one of them. The aim of our study was to evaluate the predisposition to autoimmune thyroiditis in patients with chronic hepatitis C virus during IFN-alpha therapy, depending on the presence of polymorphisms in the promoter region of CTLA-4C (−318)T gene and in exon 1 of A49G gene as well as C1858T transition of PTPN22 gene. Methods The study was conducted in 149 patients aged between 18 and 70 years (mean of 43.9 years), including 82 men and 67 women. Control group for the assessment of the distribution of analyzed polymorphism of genotypes consisted of 200 neonates, from whom umbilical blood was drawn for the tests. The patients were divided into three groups: group 1 consisted of 114 patients without thyroid impairment before and during IFN-alpha therapy, group 2 contained 9 patients with AT with the onset prior to IFN-alpha treatment, and group 3 comprised 26 patients with AT starting after the beginning of IFN-alpha therapy. Results The frequency of C1858Tand C(−318)T genotypes observed in the study group did not differ significantly from control group. A significant difference, however, was found for A49G polymorphism. Conclusions No association was demonstrated between the occurrence of autoimmune thyroiditis with the onset during IFN-alpha therapy and the presence of polymorphisms within CTLA-4 C(−318)T gene in the promoter region and A49G in exon 1, as well as C1858T transition of PTPN22 gene.

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Publié le 01 janvier 2012
Nombre de lectures 11
Langue English
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Krupińskaet al. Thyroid Research2012,5:10 http://www.thyroidresearchjournal.com/content/5/1/10
R E S E A R C H
Open Access
Association between genetic mutations and the development of autoimmune thyroiditis in patients with chronic hepatitis C treated with interferon alpha 1 2 3 1 1 ˆ Janina Krupińska , Waldemar Urbanowicz , Mariusz Kaczmarczyk , Grzegorz Kulig , Elżbieta SowińskaPrzepiera , 1 1* Elżbieta AndrysiakMamos and Anhelli Syrenicz
Abstract Background:Considerable progress was made by the introduction of interferon to the treatment of chronic hepatitis C virus infection. This treatment, however, is associated with the risk of developing or exacerbating autoimmune diseases, with chronic autoimmune thyroiditis being one of them. The aim of our study was to evaluate the predisposition to autoimmune thyroiditis in patients with chronic hepatitis C virus during IFNalpha therapy, depending on the presence of polymorphisms in the promoter region of CTLA4C (318)T gene and in exon 1 of A49G gene as well as C1858T transition of PTPN22 gene. Methods:The study was conducted in 149 patients aged between 18 and 70 years (mean of 43.9 years), including 82 men and 67 women. Control group for the assessment of the distribution of analyzed polymorphism of genotypes consisted of 200 neonates, from whom umbilical blood was drawn for the tests. The patients were divided into three groups: group 1 consisted of 114 patients without thyroid impairment before and during IFNalpha therapy, group 2 contained 9 patients with AT with the onset prior to IFNalpha treatment, and group 3 comprised 26 patients with AT starting after the beginning of IFNalpha therapy. Results:The frequency of C1858Tand C(318)T genotypes observed in the study group did not differ significantly from control group. A significant difference, however, was found for A49G polymorphism. Conclusions:No association was demonstrated between the occurrence of autoimmune thyroiditis with the onset during IFNalpha therapy and the presence of polymorphisms within CTLA4 C(318)T gene in the promoter region and A49G in exon 1, as well as C1858T transition of PTPN22 gene. Keywords:Genetic mutations, Hepatitis C virus, Interferon alpha, Thyroiditis
Background The development of autoimmune diseases is determined by the coexistence of autoimmune, environmental, and genetic factors. Genetic predisposition to autoimmune diseases depends on many genetic loci, of which three play a key role: alleles of major histocompatibility com plex genes (human leukocyte antigen HLA), mainly
* Correspondence: anhelli@asymed.ifg.pl ˆ Deceased 1 Department of Endocrinology, Metabolic Diseases and Internal Diseases, Pomeranian Medical University, Szczecin, Poland Full list of author information is available at the end of the article
class II HLADR3; alleles of a gene coding cytotoxic T lymphocyte associated antigen4 (CTLA4), and alleles of PTPN22 gene coding for lymphoidspecific tyrosine phosphatase (LYP) [1]. CTLA4 gene, located on chromosome 2q33, codes for membrane protein (cytotoxic lymphocyte antigen 4), which is important for the regulatory functions of T lym phocytes. Some variants of this gene predispose to auto immune thyroiditis, including Gravesdisease, as well as to type 1 diabetes, Addisons disease; also, such non endocrine conditions as rheumatoid arthritis or coeliac disease [27]. In order for the autoimmune response to
© 2012 Krupinska et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.