慢性丙型肝炎患者接受α干扰素治疗时基因突变与自身免疫性甲状腺炎发生之间的关联

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

作者信息

Krupińska Janina, Urbanowicz Waldemar, Kaczmarczyk Mariusz, Kulig Grzegorz, Sowińska-Przepiera Elżbieta, Andrysiak-Mamos Elżbieta, Syrenicz Anhelli

机构信息

Department of Endocrinology, Metabolic Diseases and Internal Diseases, Pomeranian Medical University, Szczecin, Poland.

出版信息

Thyroid Res. 2012 Oct 16;5(1):10. doi: 10.1186/1756-6614-5-10.

DOI:10.1186/1756-6614-5-10

PMID:23072316

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3579705/

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.

摘要

背景

干扰素被引入慢性丙型肝炎病毒感染的治疗后取得了显著进展。然而，这种治疗与自身免疫性疾病发生或加重的风险相关，慢性自身免疫性甲状腺炎就是其中之一。我们研究的目的是评估慢性丙型肝炎病毒患者在干扰素-α治疗期间发生自身免疫性甲状腺炎的易感性，这取决于细胞毒性T淋巴细胞相关抗原4（CTLA-4）C（-318）T基因启动子区域、A49G基因第1外显子的多态性以及蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因C1858T转变的存在情况。

方法

该研究纳入了149例年龄在18至70岁之间（平均43.9岁）的患者，其中男性82例，女性67例。用于评估分析基因型多态性分布的对照组由200例新生儿组成，采集他们的脐带血进行检测。患者被分为三组：第1组由114例在干扰素-α治疗前和治疗期间无甲状腺损害的患者组成，第2组包含9例在干扰素-α治疗前就已发病的自身免疫性甲状腺炎患者，第3组由26例在干扰素-α治疗开始后才发病的自身免疫性甲状腺炎患者组成。