Investigation of CLDN5 Gene 3′UTR rs10314 Polymorphism and Protein Levels in Children and Adolescents With ADHD: A Molecular and Clinical Correlation Study

Objective: This study aimed to examine the association between the rs10314 polymorphism in the 3′ untranslated region (3′UTR) of the CLDN5 gene and attention-deficit/hyperactivity disorder (ADHD), and to evaluate the serum claudin-5 levels in relation to genotype and clinical severity. Methods: A total of 323 participants were included: 159 drug-naïve children and adolescents diagnosed with ADHD and 163 age- and sex-matched healthy controls. Genotyping for rs10314 was conducted using a TaqMan® allelic discrimination assay, and serum claudin-5 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). ADHD severity was assessed using the Turgay DSM-IV-based ADHD Rating Scale. Results: Serum claudin-5 levels were significantly lower in the ADHD group compared with controls (p < 0.001), indicating potential blood–brain barrier dysfunction. The CG genotype was more common in controls (p = 0.021), suggesting a protective effect. Claudin-5 levels didn't vary across genotypes, and no correlation was observed between protein levels and clinical severity. Conclusion: This is the first study to assess both rs10314 and claudin-5 in ADHD and suggests that CLDN5 genetic variation and reduced claudin-5 expression may contribute to ADHD pathophysiology. Further studies are needed to confirm these findings and clarify their clinical implications.