R347C Polymorphisms in ADRA1A Genes and Mirtazapine Treatment Response in Koreans with Major Depression

Koo, Jahyun; Lee, Min Soo; Ham, Byungju; Won, Eun Soo

Abstract

OBJECTIVES
Adrenergic alpha 1 and 2 receptors work as pathways to control the serotonergic neuron moderation and mirtazapine acts as antagonist of these receptors. The adrenoreceptor alpha 1a (ADRA1A) gene, which encodes adrenergic alpha 1 receptor, has Arg347Cys genetic polymorphism and the polymorphism has strong relationship with many neuro-psychiatric diseases. In this study, we explored the relationship between ADRA1A R347C polymorphism and mirtazapine treatment response in Koreans with major depression.
METHODS
352 patients enrolled in this study, and the symptoms were evaluated by 17-item Hamilton Depression Rating (HAMD-17) scale. After 1, 2, 4, 8, and 12 weeks of mirtazapine treatment, the association between ADRA1A R347C polymorphism and remission/response outcomes was evaluated.
RESULTS
Treatment response to mirtazapine was significantly better in T allele carriers than C allele homozygotes after 12 weeks of mirtazapine monotherapy. The percentile decline of HAMD-17 score in T allele carriers was larger than that of C allele homozygotes. ADRA1A R347C genotypes were not significantly associated with remission.
CONCLUSIONS
The result showed that treatment response to mirtazapine was significantly associated with ADRA1A R347C genetic polymorphism. T allele carriers showed better treatment response than C allele homozygotes. It can be supposed that T allele carriers have a trend of better treatment response to mirtazapine monotherapy.