Department of Health Sciences, University of Eastern Piedmont, 28100 Novara, Italy ; Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, 28100 Novara, Italy.
Biomed Res Int. 2013;2013:471703. doi: 10.1155/2013/471703. Epub 2013 Oct 9.
TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE.
TREX1（DNase III）是一种参与氧化应激和细胞凋亡反应的外切核酸酶。TREX1 的杂合突变先前在系统性红斑狼疮（SLE）和干燥综合征（SS）患者中观察到。我们对三种自身免疫性疾病进行了 TREX1 基因的突变分析：SLE（210 例患者）和 SS（58 例患者），以确认 TREX1 在意大利人群中的参与，以及系统性硬皮病（SSc，150 例患者），因为它与 SLE 有相似之处（存在抗核抗体和结缔组织损伤）。我们观察到 7 种变异；其中两种是非同义变异（p.Glu198Lys 和 p.Met232Val）。它们分别在一名 SS 和一名 SSc 患者中被检测到，在本研究中检测的 200 名健康对照者和 1712 名已发表的对照者中均未发现。计算机分析预测这两种变异都可能对蛋白质功能有损害作用。其他 5 种变异是同义的，其中只有一种是新的（p.Pro48Pro）。本研究有助于证明 TREX1 参与自身免疫性疾病，并提出所涉及的自身免疫性疾病的范围可能更广，包括 SSc。我们不确认 TREX1 变异在 SLE 中的作用。
