Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression.
BACKGROUND
Polymorphisms in the serotonin transporter gene (5-HTT) may influence antidepressant response to selective serotonin reuptake inhibitors (SSRIs). The norepinephrine transporter (NET) is the analogous target for norepinephrine reuptake inhibitors (NRIs).


OBJECTIVE
To determine whether antidepressant responses to SSRIs or NRIs are associated with genetic polymorphisms of the corresponding monoamine transporters.


METHODS
A 6-week naturalistic treatment study with blinded outcome evaluation of 241 Korean inpatients and outpatients with major depression at an academic psychiatry service. Patients were recruited to the study from March 1998 through February 2003.


METHODS
Treatment with an SSRI (fluoxetine or sertraline; n = 136) or an NRI (nortriptyline; n = 105) antidepressant. Adherence was assessed by measuring plasma concentration at 4 weeks. Patients were genotyped for s/l polymorphisms in 5-HTT promoter region (5-HTTLPR), 5-HTT intron 2 s/l variation, and NET G1287A variation of exon 9.


METHODS
An SSRI and NRI response (defined as > or =50% decrease in Hamilton Rating Scale for Depression score at 6 weeks).


RESULTS
NRI response was associated with the NET G1287A polymorphism (odds ratio [OR], 7.54; 95% confidence interval [CI], 2.53-22.49; P<.001). An SSRI response was associated with the 5-HTT intron 2 s/l variation (OR, 20.11; 95% CI, 4.27-94.74; P<.001). The 5-HTTLPR was also associated with an SSRI response (OR, 3.34; 95% CI, 1.41-7.91; P = .006). In contrast to studies in white patients, the favorable allele for SSRI response was S 5-HTTLPR. The S 5-HTTLPR was associated also with NRI response (OR, 3.73; 95% CI, 1.32-10.53; P = .01). The NET polymorphism was not associated with an SSRI response. The NET G1287A GG genotype (56% of the population) was associated with better response to the NRI (83.3% [35/42]) than to SSRI (58.7% [44/75]) (OR, 3.52; 95% CI, 1.39-8.95; P = .006). Some genotype combinations were associated with high rates of antidepressant response and others with low rates of response.


CONCLUSIONS
Monoamine transporter gene polymorphisms were associated with response to antidepressants with homologous monoamine transporter targets. Combinations of polymorphisms were informative for response and nonresponse. Confirmation of these preliminary findings would permit refined pharmacogenetic selection of antidepressant treatment.
Kim
Hyeran
H
Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lim
Shinn-Won
SW
Kim
Seonwoo
S
Kim
Jong-Won
JW
Chang
Yun Hee
YH
Carroll
Bernard J
BJ
Kim
Doh Kwan
DK
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D009661:Nortriptyline / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use
D000928:Antidepressive Agents; D005473:Fluoxetine; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009661:Nortriptyline; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human