Comments on intron 4 VNTR polymorphism in the NOS3 gene and bipolar disorder.

We would like to discuss the recent publication by Aytac et al1 entitled ‘Association of intron 4 VNTR polymorphism in the NOS3 gene with rapid cycling and treatment resistance in bipolar disorder (BD): a case-control study.1 While BD patients with the b/b genotype and b allele had a decreased risk of rapid cycling and treatment resistance, those with the b/a genotype were more at risk for these issues, according to Aytac et al.1 Aytac et al1 also noted that the BD group with the b/b genotype experienced statistically fewer hospitalizations and higher Clinical Global ImpressionImprovement Scale scores than the BD group with the b/a and a/a genotypes.1 The effect of the studied polymorphisms might be detected in the current report. However, it is important to discuss the confounding factors in the present study. At least, there are many genetic polymorphisms that might be related to BD. Examples are UGT1A4 and UGT2B7 Polymorphisms.2 Further studies to assess the effect of those possible confounding polymorphisms should be performed.