Department of Research, Innlandet Hospital Trust, 2381 Brumunddal, Norway.
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Genes (Basel). 2023 Oct 18;14(10):1955. doi: 10.3390/genes14101955.
APOE polymorphism and the Kynurenine pathway (KP) are associated with many disorders, but little is known about associations between APOE polymorphism and the KP. This study explored the associations between the KP and APOE polymorphism in disorders associated with APOE polymorphism and changes in the KP.
Subjects with morbid obesity before and after bariatric surgery (numbers 139 and 95, respectively), depression (number 49), and unspecified neurological symptoms (number 39) were included. The following grouping of the APOE genotypes was used: E2 = ɛ2ɛ2 + ɛ2ɛ3, E3 = ɛ3ɛ3 + ɛ2ɛ4, and E4 = ɛ3ɛ4 + ɛ4ɛ4. The KP metabolites Tryptophan, Kynurenine, Kynurenic acid, Quinolinic acid, and Xanthurenic acid were quantified in serum.
The main findings were a significant positive association between E3 and Quinolinic acid (difference between E3 and E2E4: 12.0 (3.5; 18.6) ng/mL); = 0.005), and a negative association between E4 and Kynurenine (difference between E4 and E2E3: -31.3 (-54.2; -3.2) ng/mL; = 0.008). Quinolinic acid has been ascribed neurotoxic and inflammatory effects, and Kynurenine is a marker of inflammation.
The findings indicate that APOE polymorphism might cause changes in the KP that contribute to the disease. Inflammation could be the link between APOE and the KP.
载脂蛋白 E 多态性和犬尿氨酸途径（KP）与许多疾病有关，但对载脂蛋白 E 多态性与 KP 之间的关联知之甚少。本研究探讨了与载脂蛋白 E 多态性相关的疾病中 KP 与载脂蛋白 E 多态性之间的关联，以及 KP 的变化。
纳入了肥胖症患者（术前 139 例，术后 95 例）、抑郁症患者（49 例）和不明原因神经症状患者（39 例）。采用以下载脂蛋白 E 基因型分组：E2=ɛ2ɛ2+ɛ2ɛ3，E3=ɛ3ɛ3+ɛ2ɛ4，E4=ɛ3ɛ4+ɛ4ɛ4。对血清中色氨酸、犬尿氨酸、犬尿喹啉酸、喹啉酸和黄嘌呤酸等 KP 代谢物进行定量分析。
主要发现是 E3 与喹啉酸之间存在显著正相关（E3 与 E2E4 之间的差异：12.0（3.5；18.6）ng/mL； = 0.005），E4 与犬尿氨酸之间存在负相关（E4 与 E2E3 之间的差异：-31.3（-54.2；-3.2）ng/mL； = 0.008）。喹啉酸具有神经毒性和炎症作用，犬尿氨酸是炎症的标志物。
研究结果表明，载脂蛋白 E 多态性可能导致 KP 发生变化，从而导致疾病发生。炎症可能是载脂蛋白 E 与 KP 之间的联系。
