Rajula Hema Sekhar Reddy, Piras Cristina, Kopeć Karolina Krystyna, Noto Antonio, Spada Martina, Lilliu Katia, Manchia Mirko, Mussap Michele, Atzori Luigi, Fanos Vassilios
Department of Surgical Sciences, University of Cagliari, 09042 Cagliari, Italy.
Ph.D. Student Marie Sklodowska-Curie CAPICE Project, Department of Surgical Sciences, University of Cagliari, 09042 Cagliari, Italy.
Metabolites. 2025 Aug 15;15(8):551. doi: 10.3390/metabo15080551.
This study investigates metabolic perturbations in serum samples associated with different genotypes (AA, AC, and CC) of the schizophrenia susceptibility gene NOS1AP-rs12742393.
Publicly available datasets acquired using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) were analyzed by employing network and enrichment approaches.
Key metabolites, including tryptophan, 2-aminobutyric acid, palmitic acid, and 5-hydroxytryptophan, were strongly linked to metabolic networks in genotypes AA-AC and AA. Enrichment analysis was conducted to identify metabolite sets differentially distributed across these genotypes, with a particular focus on genotype AA.
The findings suggest that NOS1AP-rs12742393 contributes to complex metabolic alterations involving amino acids, organic compounds, fatty acids, and cholic acids. Moreover, serum metabolome analysis demonstrates sufficient sensitivity and specificity to provide insights into NOS1AP-rs12742393 genotype-associated metabolic profiles, supporting a network-based approach to understanding schizophrenia susceptibility.
本研究调查了与精神分裂症易感基因NOS1AP - rs12742393的不同基因型（AA、AC和CC）相关的血清样本中的代谢紊乱情况。
采用网络和富集方法分析通过超高效液相色谱 - 四极杆飞行时间质谱（UPLC - QTOFMS）获得的公开可用数据集。
关键代谢物，包括色氨酸、2 - 氨基丁酸、棕榈酸和5 - 羟色氨酸，与AA - AC和AA基因型的代谢网络密切相关。进行富集分析以确定在这些基因型中差异分布的代谢物集，特别关注AA基因型。
研究结果表明，NOS1AP - rs12742393导致涉及氨基酸、有机化合物、脂肪酸和胆酸的复杂代谢改变。此外，血清代谢组分析显示出足够的敏感性和特异性，能够深入了解与NOS1AP - rs12742393基因型相关的代谢谱，支持基于网络的方法来理解精神分裂症易感性。
