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

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.

Figure 1

Identification of RS 231775 polymorphism of CTLA4 gene. Lanes: M – DNA length marker (Puc Mix Marker 8, MBI Fermentas), 1 – amplicon (162 bp) not subject to restriction, 2, 4, 5 – AA homozygotes, 3 – GG homozygote, 6 – AG heterozygote.

Figure 2

Identification of rs2476601 polymorphism of PTPN22 gene. Lanes: M – DNA length marker (Puc Mix Marker 8, MBI Fermentas), 1, 8, 9, 10 – CT heterozygotes, 2, 11 – TT homozygotes, 3, 4, 5, 6, 7, 12 – CC homozygotes.

Figure 3

Identification of rs5742909 polymorphism of CTLA4 gene. Lanes: M – DNA length marker (pUC Mix Marker 8, MBI Fermentas), 1, 2, 7 – CT heterozygotes, 3, 4, 5, 6, 8, 9, 10, 11, 12, 14 – CC homozygotes, 13 – TT homozygote.