Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response.
BACKGROUND
Serotonin transporter (5-HTT) and norepinephrine transporter (NET) are the primary targets of many antidepressants. We aimed to determine the potential correlations of 5-HTT/NET gene polymorphisms with the susceptibility to depression and the antidepressant response to selective serotonin reuptake inhibitors (SSRIs) or dual selective serotonin/norepinephrine reuptake inhibitors (SNRIs).


METHODS
A total of 579 depressed patients and 437 healthy controls, all of Chinese Han region, were collected and genotyped by polymerase chain reactions (PCR). All patients were under treatment of SSRI or SNRI for 6 weeks, and were evaluated using a 17-item Hamilton Depression Rating Scale (HAMD).


RESULTS
Five hundred sixty-seven of 579 patients completed the total treatment, of which 362 were in SSRI and 205 in SNRI group. It was shown that the NET-T182C, interacting with 5-HTTLPR, was associated with the susceptibility to depression. Patients with both NET-T182C C/C and 5-HTTLPR S/S genotypes had lower baseline HAMD scores. Patients with 5-HTTLPR L/L or STin2 12/12 genotype experienced better clinical response to the SSRI treatment. Besides, the STin2 12/12 carriers showed a superior reduction to HAMD scores over treatment period. No correlation between NET T182C/G1287A polymorphisms and antidepressant response was observed.


CONCLUSIONS
Our study revealed a positive association of the NET-T182C polymorphism with susceptibility to and severity of depression, and a positive association between the 5-HTT polymorphisms and the antidepressant response to SSRI. Combinations of these polymorphisms provided some potential gene-gene interaction effects. These findings might be of some clinical values in optimization of depression treatment.
Min
Wenjiao
W
Mental Health Center, West China Hospital, Sichuan University, and Chengdu Fourth People's Hospital, Chengdu 610041, People's Republic of China.
Li
Tao
T
Ma
Xiaohong
X
Li
Zhengyu
Z
Yu
Tao
T
Gao
Dong
D
Zhang
Bo
B
Yun
Yang
Y
Sun
Xueli
X
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000328:Adult; D044466:Asian People; D002681:China; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D009435:Synaptic Transmission
D018759:Adrenergic Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human