Plasminogen activator inhibitor 1 gene polymorphisms and mirtazapine responses in Koreans with major depression

초록

Introduction: Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mental disorders and in the mechanism of action of antidepressant medications. The mature form of BDNF is derived from proBDNF through tissue type plasminogen activator (tPA) and the plasminogen system in the brain, which is regulated by an endogenous inhibitor, plasminogen activator inhibitor (PAI). Therefore, PAI may be involved in the development of major depressive disorder (MDD) and its response to antidepressant treatment. The present study determined the relationship between the 4G/5G polymorphism in the PAI1 gene and the clinical outcome of mirtazapine treatment in 271 Korean MDD patients. Methods: We tested the association between the polymorphism and response to mirtazapine treatment or percentage decrease of the 21-item Hamilton Depression Rating (HAMD21) scores using multiple logistic and linear regression analysis. Results: PAI1 4G/5G genotypes and allele distributions were comparable between responders and non-responders during the treatment period. Similarly, linear regression showed no association between genotypes or alleles and the percentage decline in total HAMD21 with mirtazapine treatment. In the analysis of symptomatic subscores, the percentage decline in the psychic anxiety and delusion scores after 4 weeks of mirtazapine treatment showed a statistical trend to a difference among genotypes, although it was not statistically significance. Discussion: In this first pharmacogenetics study of the PAI1 4G/5G polymorphism and mirtazapine treatment response, our results do not support the hypothesis that this polymorphism is involved in the therapeutic response to mirtazapine.

키워드