Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
Clin Exp Rheumatol. 2020 Sep-Oct;38(5):949-955. Epub 2020 Mar 10.
The TYK2 gene encodes a tyrosin kinase which is involved in multiple immune functions. A functional variant of this gene has been identified to play a protective role in multiple autoimmune diseases. The goal of this study was to evaluate the involvement of this variant of TYK2 in vasculitides [giant cell arteritis (GCA), ANCA-associated vasculitis (AAV) and IgA vasculitis (IgAV)] and viral infections [hepatitis C virus (HCV) and human immunodeficiency virus type I (HIV-1)].
The study sample was composed of 13,745 European individuals. The genotyping was performed by Immunochip and TaqMan 5' allele discrimination assays and the allele frequencies were compared using PLINK.
Although the results obtained did not reach the genome-wide level of significance, p-values at nominal significance were observed, suggesting that the TYK2 variant provides protection against two vasculitides: GCA (p=5.94E-3; OR (95%CI) = 0.56 (0.37-0.85) and AAV (p=6.79E-3; OR (95%CI) = 0.65 (0.47-0.89). However, this variant was not found to be associated with IgAV. No evidence was gained that the TYK2 variant confers susceptibility to HCV and HIV-1 infection.
This is the first study to propose the association between the TYK2 and both GCA and AAV. Our findings also suggest that TYK2 does not play a relevant role in IgAV or in susceptibility to HCV and HVI-1.
TYK2 基因编码一种酪氨酸激酶，参与多种免疫功能。该基因的一种功能变体已被确定在多种自身免疫性疾病中发挥保护作用。本研究的目的是评估该 TYK2 变体在血管炎（巨细胞动脉炎（GCA）、抗中性粒细胞胞浆抗体相关性血管炎（AAV）和 IgA 血管炎（IgAV））和病毒感染（丙型肝炎病毒（HCV）和人类免疫缺陷病毒 I 型（HIV-1））中的作用。
研究样本由 13745 名欧洲个体组成。通过 Immunochip 和 TaqMan 5'等位基因区分检测进行基因分型，使用 PLINK 比较等位基因频率。
尽管获得的结果未达到全基因组水平的显著性，但观察到名义显著性的 p 值，表明 TYK2 变体可提供对两种血管炎的保护作用：GCA（p=5.94E-3；OR（95%CI）=0.56（0.37-0.85）和 AAV（p=6.79E-3；OR（95%CI）=0.65（0.47-0.89）。然而，该变体与 IgAV 无关。没有证据表明 TYK2 变体易感染 HCV 和 HIV-1。
这是第一项提出 TYK2 与 GCA 和 AAV 相关的研究。我们的研究结果还表明，TYK2 在 IgAV 或 HCV 和 HIV-1 易感性中不起重要作用。
