Serotonin-Related Polymorphisms in TPH1 and HTR5A Genes Are Not Associated with Escitalopram Treatment Response in Korean Patients with Major Depression

Abstract

Background/Aims: The genetic variations in serotonin-related genes may be associated with antidepressant treatment response in major depressive disorder (MDD). The tryptophan hydroxylase-1 (TPH1) gene and serotonin 5A receptor (HTR5A) gene are known to be involved in serotonin biosynthesis and signal transduction, respectively. The purpose of this study was to investigate a possible interaction between the TPH1 gene and the HTR5A gene in the treatment outcome of escitalopram in MDD. Methods: In total, 245 patients diagnosed with MDD were recruited, and their symptoms were evaluated using the 17-item Hamilton Depression Rating scale (HAMD-17). The association between the TPH1 218A/C and HTR5A 12A/T polymorphisms and the clinical outcomes (remission, response and changes in HAMD-17 score) was investigated after 2, 4 and 8 weeks of escitalopram treatment using multiple logistic regression or multiple linear regression analysis. Results: No significant associations of TPH1 or HTR5A gene polymorphisms were observed with either response rate or remission rate at 2, 4 and 8 weeks after escitalopram treatment. In addition, the gene-gene interaction between TPH1 and HTR5A genes was not associated with the treatment outcome. Conclusions: Our results suggest that TPH1 218A/C and HTR5A 12A/T polymorphisms cannot predict treatment response in major depression.

Advances in Biomarkers of Major Depressive Disorder

“…Another study found that marked interaction between CC genotype and remission status was associated with endpoint harm avoidance score [75]. A Korean study found that TPH1 218A/C polymorphisms did not predict treatment response in MDD [68]. To our knowledge, epigenetic studies on TPH1 have not been published.…”

“…In another large study of 760 adult patients with moderate-to-severe depression, several variants in HTR2A-predicted response to SSRIs escitalopram with one marker rs9316233 and explained 1.1% of variance [64]. Unfortunately, HTR2A polymorphism association with treatment response has not been replicated [65][66][67][68]. Meta-analysis found that HTR2A SNP rs6311 did not confer increased risk to MDD [69].…”