Association of intron 4 VNTR polymorphism in the NOS3 gene with rapid cycling and treatment resistance in bipolar disorder: a case-control study

Objective: To evaluate the relationship between patients' clinical parameters, especially clinical specifiers, and the intron 4 VNTR variant of the endothelial nitric oxide synthase (NOS3) gene in bipolar disorder (BD) patients. Methods: A sample of 95 patients with BD and 95 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient psychiatry clinic for 6 months and were evaluated with some scales for clinical parameters. In addition, PCR was used to determine the NOS3 intron 4 VNTR variant. Results: The NOS3 genotype and allele frequency distributions of rapid cycling BD patients were significantly different from non-rapid cycling BD patients and the control groups. Furthermore, NOS3 genotype and allele frequency distributions of treatment-resistant BD patients were significantly different from treatment-responsive BD patients and the control groups. While BD patients carrying the b/b genotype and b allele had a lower risk of rapid cycling and treatment resistance, having the b/a genotype in BD patients was at higher risk in terms of rapid cycling and treatment resistance. In addition, the number of hospitalizations and the Clinical Global Impression-Improvement Scale scores of the BD group with the b/b genotype were statistically lower than the BD group with b/a and a/a genotypes. Conclusions: We propose that the intron 4 VNTR variant of the NOS3 gene may be associated with rapid cycling and treatment resistance in Turkish patients diagnosed with BD.

Automated summary

This study evaluated the relationship between clinical parameters of bipolar disorder patients and the intron 4 VNTR variant of the endothelial nitric oxide synthase (NOS3) gene. The results suggest that the NOS3 intron 4 VNTR variant may be associated with rapid cycling and treatment resistance in bipolar disorder patients.