Objectives rs76428106-C, a low frequency polymorphism that affects the splicing of the FLT3 gene, has recently been associated with several seropositive autoimmune diseases. Here, we aimed to evaluate the potential implication of rs76428106-C in the susceptibility to systemic sclerosis (SSc). Methods We analysed a total of 26 598 European ancestry individuals, 9063 SSc and 17 535 healthy controls, to test the association between FLT3 rs76428106-C and SSc and its different subphenotypes. Genotype data of rs76428106 were obtained by imputation of already available genome-wide association study data and analysed by logistic regression analysis. Results In accordance with that observed in other autoimmune disorders, the FLT3 rs76428106-C allele was significantly increased [P-value = 2.03 × 10−3, odds ratio (OR) = 1.34] in SSc patients compared with healthy controls. A similar risk effect was found when the main SSc clinical and serological subgroups were compared with controls. When comparing SSc patients with and without digital ulcers (DU), the rs76428106-C frequency was significantly increased in DU-positive SSc patients in comparison with DU-negative patients (P-value = 0.036, OR = 2.16). Conclusion This study is the first to report an association between rs76428176-C and SSc. Our results support the role of FLT3 as a relevant gene in seropositive immune-mediated diseases and a potential biomarker for SSc microangiopathy.

中文翻译：

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FLT3 功能性低频变异 rs76428106-C 与系统性硬化症的易感性相关

目的 rs76428106-C 是一种影响 FLT3 基因剪接的低频多态性，最近与多种血清阳性自身免疫性疾病有关。在这里，我们旨在评估 rs76428106-C 在系统性硬化症 (SSc) 易感性中的潜在意义。方法 我们分析了总共 26 598 名欧洲血统个体、9 063 名 SSc 和 17 535 名健康对照，以检验 FLT3 rs76428106-C 和 SSc 及其不同亚表型之间的关联。rs76428106 的基因型数据是通过对已有的全基因组关联研究数据进行插补获得的，并通过逻辑回归分析进行了分析。结果 根据在其他自身免疫性疾病中观察到的结果，FLT3 rs76428106-C 等位基因显着增加 [P 值 = 2.03 × 10-3，比值比 (OR) = 1。34] 在 SSc 患者中与健康对照相比。当将主要的 SSc 临床和血清学亚组与对照组进行比较时，发现了类似的风险效应。当比较有和没有手指溃疡 (DU) 的 SSc 患者时，与 DU 阴性患者相比，DU 阳性 SSc 患者的 rs76428106-C 频率显着增加（P 值 = 0.036，OR = 2.16）。结论 本研究首次报告了 rs76428176-C 与 SSc 之间的关联。我们的结果支持 FLT3 作为血清阳性免疫介导疾病中的相关基因和 SSc 微血管病的潜在生物标志物的作用。与 DU 阴性患者相比，DU 阳性 SSc 患者的 rs76428106-C 频率显着增加（P 值 = 0.036，OR = 2.16）。结论 本研究首次报告了 rs76428176-C 与 SSc 之间的关联。我们的结果支持 FLT3 作为血清阳性免疫介导疾病中的相关基因和 SSc 微血管病的潜在生物标志物的作用。与 DU 阴性患者相比，DU 阳性 SSc 患者的 rs76428106-C 频率显着增加（P 值 = 0.036，OR = 2.16）。结论 本研究首次报告了 rs76428176-C 与 SSc 之间的关联。我们的结果支持 FLT3 作为血清阳性免疫介导疾病中的相关基因和 SSc 微血管病的潜在生物标志物的作用。