Rare Variants in the TREX1 Gene and Susceptibility to Autoimmune Diseases
Rare Variants in the TREX1 Gene and Susceptibility to Autoimmune Diseases
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DOI：
10.1155/2013/471703
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发表时间：
2013-01-01
影响因子：
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通讯作者：
D'Alfonso, Sandra
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文献类型：
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作者：
Barizzone, Nadia;Monti, Sara;D'Alfonso, Sandra
TREX1(DNase III)是一种参与氧化应激和细胞凋亡反应的核酸外切酶。TREX1杂合突变以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基因突变分析：SLE(210名患者)和SS(58名患者)，以确认TREX1在意大利人群中的参与，以及系统性硬化症(SSC，150名患者)，因为它与SLE相似(存在抗核抗体和结缔组织损伤)。我们观察到7个变异；其中两个是新的非同义变异(p.Glu198Lys和p.Met232Val)。在一名SS和一名SSC患者中分别检测到它们，在这项研究中输入的200名健康对照和1712名已发表的对照中没有一人检测到它们。在计算机分析中预测，这两个变种可能会对蛋白质功能产生破坏性作用。其他5个变种是同义的，只有一个是新的(p.Pro48Pro)。这项研究有助于证明TREX1与自身免疫性疾病有关，并提出所涉及的自身免疫性疾病的范围可以更广，包括SSC。我们不确定TREX1变异体在SLE中的作用。
TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygousmutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). We performed amutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirma 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.