Altered expression of KCNQ1OT1 and ZEB1-AS1 lncRNAs in autism spectrum disorder: A case–control study

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a significant genetic basis, although its multifactorial etiology remains poorly understood. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in gene regulation and in modulating key signaling pathways, including extracellular matrix (ECM), which are crucial for neural development.

In this study, we examined the expression levels of three lncRNAs; TGFβ2-AS1, KCNQ1OT1, and ZEB1-AS1; in peripheral blood samples collected from 30 individuals with ASD and 41 age and gender matched healthy controls. Total RNA was extracted, and gene expression was quantified using real-time quantitative PCR.

The results revealed a significant upregulation of ZEB1-AS1 (approximately 20-fold increase, p < 0.0001) and a striking downregulation of KCNQ1OT1 (nearly 30-fold decrease, p < 0.0001) in ASD patients. In contrast, TGFβ2-AS1 expression showed no significant change. A positive correlation was also observed between KCNQ1OT1 expression and patient age. Receiver operating characteristic (ROC) curve analyses demonstrated strong diagnostic potential for KCNQ1OT1 and ZEB1-AS1, with AUC values of 0.91 and 0.88, respectively.

Overall, these findings suggest that dysregulation of specific lncRNAs may contribute to ASD pathogenesis and highlight KCNQ1OT1 and ZEB1-AS1 as promising diagnostic biomarkers and potential therapeutic targets.