Impact of rs174537 on Critically Ill Patients with Acute Lung Injury: A Secondary Analysis of the OMEGA Randomized Clinical Trial.
Impact of rs174537 on Critically Ill Patients with Acute Lung Injury: A Secondary Analysis of the OMEGA Randomized Clinical Trial.
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DOI：
10.1093/cdn/nzaa147
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发表时间：
2020-10
影响因子：
4.8
通讯作者：
Rahbar E
中科院分区：
文献类型：
--
作者：
Dosso B;Waits CMK;Simms KN;Sergeant S;Files DC;Howard TD;Langefeld CD;Chilton FH;Rahbar E
重症监护病房的营养对于患者护理至关重要;然而，对于急性呼吸窘迫综合征患者，富含PUFA（如γ-亚麻酸（GLA）、EPA和DHA）的免疫调节饮食仍存在争议。我们假设影响PUFA代谢的遗传变异有助于对富含PUFA的饮食的混合反应。在这项研究中，我们的目的是测试单核苷酸多态性（SNP）rs 174537对富含PUFA饮食的差异反应的影响。我们对OMEGA试验（NCT 00609180）进行了二次分析，其中129名受试者接受安慰剂对照饮食，143名接受omega油。从血沉棕黄层提取DNA并用于rs 174537基因分型;血浆用于定量PUFA。我们测试了SNP-饮食对PUFA浓度、炎症生物标志物和患者结局的相互作用。我们观察到，所有接受欧米茄油的个体都显示出显著更高的GLA、EPA和DHA浓度（所有P < 0.0001），但它们在rs 174537基因型之间没有变化。在非裔美国人的循环DHA浓度上观察到统计学显著的SNP-饮食相互作用。具体而言，服用安慰剂的非裔美国人T等位基因携带者显示DHA浓度升高。此外，接受omega油的所有个体均具有较高浓度的EPA衍生的尿F3-异前列烷（高加索人：P = 0.0011;非裔美国人：P = 0.0002）。尽管有这些发现，我们没有检测到任何显著的SNP-饮食相互作用对肺功能指标，临床结果和死亡率。这项研究强调了遗传和种族对PUFA代谢和炎症的重要性。特别是，rs 174537对循环DHA和尿异前列烷浓度有显著影响。鉴于我们的样本量相对较小，需要在更大的多种族队列中进行进一步研究，以评估rs 174537对脂肪酸代谢和下游炎症的影响。这项研究揭示了rs 174537对急性肺损伤或急性呼吸窘迫综合征（ARDS）患者对富含omega的饮食和炎症的不同反应的影响。rs 174537与ARDS患者循环DHA和尿异前列烷水平的改变有关。
Nutrition in the intensive care unit is vital for patient care; however, immunomodulatory diets rich in PUFAs like γ-linolenic acid (GLA), EPA, and DHA remain controversial for patients with acute respiratory distress syndrome. We postulate that genetic variants impacting PUFA metabolism contribute to mixed responses to PUFA-rich diets. In this study, we aimed to test the effects of single nucleotide polymorphism (SNP) rs174537 on differential responses to PUFA-rich diets. We performed a secondary analysis of the OMEGA trial (NCT00609180) where 129 subjects received placebo control diets and 143 received omega-oil. DNA was extracted from buffy coats and used to genotype rs174537; plasma was used to quantitate PUFAs. We tested for SNP–diet interactions on PUFA concentrations, inflammatory biomarkers, and patient outcomes. We observed that all individuals receiving omega-oil displayed significantly higher concentrations of GLA, EPA, and DHA (all P < 0.0001), but they did not vary by genotype at rs174537. Statistically significant SNP–diet interactions were observed on circulating DHA concentrations in African Americans. Specifically, African American T-allele carriers on placebo illustrated elevated DHA concentrations. Additionally, all individuals receiving omega-oil had higher concentrations of EPA-derived urinary F3-isoprostane (Caucasians: P = 0.0011; African Americans: P = 0.0002). Despite these findings, we did not detect any significant SNP–diet interactions on pulmonary functional metrics, clinical outcomes, and mortality. This study highlights the importance of genetic and racial contributions to PUFA metabolism and inflammation. In particular, rs174537 had a significant impact on circulating DHA and urinary isoprostane concentrations. Given our relatively small sample size, further investigations in larger multiethnic cohorts are needed to evaluate the impact of rs174537 on fatty acid metabolism and downstream inflammation. This study reveals new insights on the impact of rs174537 on differential responses to omega-rich diets, and inflammation in patients with acute lung injury or acute respiratory distress syndrome (ARDS). rs174537 was associated with altered levels of circulating DHA and urinary isoprostanes in ARDS patients.
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