Genetic variants of the three-prime repair exonuclease 1 (TREX1) -an exonuclease involved in DNA repair and degradation- have been previously found to increase susceptibility to Aicardi Goutieres syndrome, familial chilblain lupus and systemic lupus erythematosus. We aimed to explore whether TREX1 common variants could influence the risk of primary Sjogren's syndrome (SS) and SS-related lymphoma. Three single nucleotide polymorphisms (SNPs) of the TREX1 gene (rs11797, rs3135941 and rs3135945) were evaluated in 229 SS, 89 SS-lymphoma (70 SS-MALT and 19 SS non-MALT) and 240 healthy controls by PCR-based assays. In available 52 peripheral blood and 26 minor salivary gland tissues from our SS cohort, mRNA expression of type I interferon (IFN) related genes and TREX1 was determined by real-time PCR. Significantly decreased prevalence of rs11797 A minor allele was detected in SS patients complicated by non-MALT lymphoma compared to controls (ΟR [95% CI]: 0.4 [0.2-0.9], p-value: 0.02). SS patients carrying the rs11797 AA genotype had increased type I IFN related gene mRNA expression in minor salivary gland tissues. These data support genetically related dampened type I IFN production as an additional mechanism for SS-related lymphomagenesis.

中文翻译：

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干燥综合征相关淋巴瘤发生中的 TREX1 变异

三原修复外切核酸酶 1 (TREX1) 的遗传变体 - 一种参与 DNA 修复和降解的外切核酸酶 - 先前已被发现会增加对 Aicardi Goutieres 综合征、家族性冻疮狼疮和系统性红斑狼疮的易感性。我们旨在探讨 TREX1 常见变异是否会影响原发性干燥综合征 (SS) 和 SS 相关淋巴瘤的风险。TREX1 基因的三个单核苷酸多态性 (SNP)（rs11797、rs3135941 和 rs3135945）在 229 个 SS、89 个 SS 淋巴瘤（70 个 SS-MALT 和 19 个 SS 非 MALT）和 240 个健康对照中通过基于 PCR 的测定进行评估。在来自我们 SS 队列的 52 份外周血和 26 份小唾液腺组织中，通过实时 PCR 确定了 I 型干扰素 (IFN) 相关基因和 TREX1 的 mRNA 表达。与对照组相比，在并发非 MALT 淋巴瘤的 SS 患者中检测到 rs11797 A 次要等位基因的患病率显着降低（ΟR [95% CI]：0.4 [0.2-0.9]，p 值：0.02）。携带rs11797 AA基因型的SS患者小唾液腺组织中I型干扰素相关基因mRNA表达增加。这些数据支持遗传相关的抑制 I 型 IFN 产生作为 SS 相关淋巴瘤发生的附加机制。