Nephrology Division and Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Division of Precision Medicine, New York University School of Medicine, New York, NY, USA.
Commun Biol. 2023 Jul 31;6(1):792. doi: 10.1038/s42003-023-05159-5.
Eicosanoids are biologically active derivatives of polyunsaturated fatty acids with broad relevance to health and disease. We report a genome-wide association study in 8406 participants of the Atherosclerosis Risk in Communities Study, identifying 41 loci associated with 92 eicosanoids and related metabolites. These findings highlight loci required for eicosanoid biosynthesis, including FADS1-3, ELOVL2, and numerous CYP450 loci. In addition, significant associations implicate a range of non-oxidative lipid metabolic processes in eicosanoid regulation, including at PKD2L1/SCD and several loci involved in fatty acyl-CoA metabolism. Further, our findings highlight select clearance mechanisms, for example, through the hepatic transporter encoded by SLCO1B1. Finally, we identify eicosanoids associated with aspirin and non-steroidal anti-inflammatory drug use and demonstrate the substantial impact of genetic variants even for medication-associated eicosanoids. These findings shed light on both known and unknown aspects of eicosanoid metabolism and motivate interest in several gene-eicosanoid associations as potential functional participants in human disease.
类二十烷酸是多不饱和脂肪酸的生物活性衍生物，与健康和疾病有广泛的关联。我们在动脉粥样硬化风险社区研究的 8406 名参与者中进行了全基因组关联研究，确定了 41 个与 92 种类二十烷酸和相关代谢物相关的位点。这些发现突出了类二十烷酸生物合成所需的位点，包括 FADS1-3、ELOVL2 和许多 CYP450 位点。此外，重要的关联暗示了一系列非氧化脂质代谢过程在类二十烷酸调节中的作用，包括 PKD2L1/SCD 和几个参与脂肪酸辅酶 A 代谢的位点。此外，我们的发现突出了一些清除机制，例如通过 SLCO1B1 编码的肝脏转运蛋白。最后，我们确定了与阿司匹林和非甾体抗炎药使用相关的类二十烷酸，并证明了遗传变异的巨大影响，即使对于与药物相关的类二十烷酸也是如此。这些发现揭示了类二十烷酸代谢的已知和未知方面，并激发了对几种基因-类二十烷酸关联作为人类疾病潜在功能参与者的兴趣。
