The rs139226362 (delGATT) variant in the NTS gene alters plasma neurotensin levels in schizophrenia

Abstract

Neurotensin (NTS) is a critical neuropeptide involved in multiple pathways in the central nervous and peripheral systems. We assessed the possible functional relevance of NTS in SCZ pathogenesis by focusing on the rs139226362 (delGATT) located in the 3' untranslated region (UTR) of the NTS. A total of 88 Turkish individuals with known genotypes for the delGATT allele were included in the study. Differences in NTS mRNA expression and circulating NTS protein levels were evaluated by RT-qPCR and ELISA, respectively. The stability of RNA secondary structures and the binding patterns of RNA-binding protein (RBPs) interactions were evaluated by analysis. Plasma NTS protein levels were significantly higher ( = 0.0003) in SCZ patients carrying the delGATT variant compared to those with wild-type genotype. This genotype-protein association was not observed in healthy controls, indicating a disease-specific effect. Moreover, plasma NTS levels were correlated with PANSS scores ( = -0.290, = 0.041) and BMI ( = 0.306, = 0.031) in SCZ patients. These findings suggest that rs139226362 may influence post-transcriptional regulation, with the indel potentially associated with milder SCZ symptoms through altered molecular pathways. Further validation in experimental models may support the development of NTS-based personalized treatment strategies for SCZ management.