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.