Dosso Beverly, Waits Charlotte Mae K, Simms Kelli N, Sergeant Susan, Files D Clark, Howard Timothy D, Langefeld Carl D, Chilton Floyd H, Rahbar Elaheh
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Department of Biomedical Engineering, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Winston-Salem, NC, USA.
Curr Dev Nutr. 2020 Sep 14;4(10):nzaa147. doi: 10.1093/cdn/nzaa147. eCollection 2020 Oct.
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 < 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: = 0.0011; African Americans: = 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.
重症监护病房的营养对于患者护理至关重要；然而，富含多不饱和脂肪酸（PUFA）如γ-亚麻酸（GLA）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的免疫调节饮食对于急性呼吸窘迫综合征患者仍存在争议。我们推测，影响PUFA代谢的基因变异导致了对富含PUFA饮食的混合反应。
在本研究中，我们旨在测试单核苷酸多态性（SNP）rs174537对富含PUFA饮食差异反应的影响。
我们对OMEGA试验（NCT00609180）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ω-油。从血沉棕黄层中提取DNA并用于对rs174537进行基因分型；血浆用于定量PUFA。我们测试了SNP-饮食相互作用对PUFA浓度、炎症生物标志物和患者结局的影响。
我们观察到，所有接受ω-油的个体的GLA、EPA和DHA浓度均显著升高（均<0.0001），但它们在rs174537位点的基因型上没有差异。在非裔美国人的循环DHA浓度上观察到了具有统计学意义的SNP-饮食相互作用。具体而言，接受安慰剂治疗的非裔美国T等位基因携带者的DHA浓度升高。此外，所有接受ω-油的个体的EPA衍生的尿F3-异前列腺素浓度更高（白种人：=0.0011；非裔美国人：=0.0002）。尽管有这些发现，但我们未检测到在肺功能指标、临床结局和死亡率方面存在任何显著的SNP-饮食相互作用。
本研究强调了基因和种族对PUFA代谢及炎症的重要性。特别是，rs174537对循环DHA和尿异前列腺素浓度有显著影响。鉴于我们的样本量相对较小，需要在更大的多民族队列中进行进一步研究，以评估rs174537对脂肪酸代谢和下游炎症的影响。
