Sphingosine-1-phosphate (S1P) is a signaling phospholipid involved in pathophysiologic progression of acute respiratory distress syndrome (ARDS) through its roles in endothelial barrier function and immune modulation. We hypothesized that decreased serum S1P level is associated with the clinical outcomes of ARDS and polymorphisms in the S1P gene are associated with serum S1P levels. This multicenter prospective study includes ARDS patients and healthy blood donors as controls. Serum S1P levels were quantified using enzyme-linked immunosorbent assays. Eight tag single nucleotide polymorphisms (SNPs) in the S1P gene were detected, and their associations with S1P levels were evaluated. A total of 121 ARDS patients and 100 healthy individuals were enrolled. Serum S1P levels were lower in ARDS patients than in controls (P < 0.001). Decreased S1P levels correlated with more organ dysfunction and higher Acute Physiology and Chronic Health Evaluation II scores. Changes in S1P levels in ARDS patients were associated with the clinical outcomes. The recessive model for SNP rs3743631 suggests that GG homozygote is associate with a higher risk for ARDS. The dominant model for SNP rs907045 suggests that AA or TA genotype might increase the risk for ARDS. In ARDS patients, the rs3743631 GG genotype showed lower S1P levels than those harboring AG and AA genotypes. The serum S1P levels of rs907045 AA or TA genotype patients were lower than those of TT genotype. Serum S1P levels are dramatically decreased in ARDS patients. Reduced S1P levels are associated with worse clinical outcomes. There is a significant association between S1P rs3743631, rs907045 polymorphisms and susceptibility of ARDS.

中文翻译：

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急性呼吸窘迫综合征中的血清 1-磷酸鞘氨醇水平和 1-磷酸鞘氨醇基因多态性：一项多中心前瞻性研究。

Sphingosine-1-phosphate (S1P) 是一种信号磷脂，通过其在内皮屏障功能和免疫调节中的作用参与急性呼吸窘迫综合征 (ARDS) 的病理生理学进展。我们假设血清 S1P 水平降低与 ARDS 的临床结果相关，并且 S1P 基因的多态性与血清 S1P 水平相关。这项多中心前瞻性研究包括 ARDS 患者和健康献血者作为对照。使用酶联免疫吸附测定法量化血清 S1P 水平。检测到 S1P 基因中的八个标记单核苷酸多态性 (SNP)，并评估了它们与 S1P 水平的关联。共招募了 121 名 ARDS 患者和 100 名健康人。ARDS 患者的血清 S1P 水平低于对照组（P < 0.001）。降低的 S1P 水平与更多的器官功能障碍和更高的急性生理学和慢性健康评估 II 评分相关。ARDS 患者 S1P 水平的变化与临床结果相关。SNP rs3743631 的隐性模型表明 GG 纯合子与较高的 ARDS 风险相关。SNP rs907045 的显性模型表明 AA 或 TA 基因型可能会增加 ARDS 的风险。在 ARDS 患者中，rs3743631 GG 基因型显示出比携带 AG 和 AA 基因型的患者更低的 S1P 水平。rs907045 AA或TA基因型患者血清S1P水平低于TT基因型患者。ARDS 患者的血清 S1P 水平显着降低。S1P 水平降低与较差的临床结果相关。S1P rs3743631、