Monoamine Transporter Gene Polymorphisms and Antidepressant Response in Koreans With Late-Life Depression

Kim, Hye‐Ran; Lim, Seong Woo; Kim, Seonwoo; Kim, Jong-Won; Chang, Yun Hee; Carroll, Bernard J.; Kim, Doh Kwan

doi:10.1001/jama.296.13.1609

Cited by 185 publications

(144 citation statements)

References 52 publications

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“…24 Interestingly, the G/G genotype was also reported to be associated with favorable response to norepinephrine uptake inhibitors (nortriptyline) in depressed patients (P < 0.001). 37 The results for these three SNPs (rs3785157, rs5569 and rs998424) were not significant in our study (P > 0.05).…”

Section: Discussioncontrasting

confidence: 67%

Further evidence of association between two NET single-nucleotide polymorphisms with ADHD

et al. 2007

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The norepinephrine transporter (NET) gene is an attractive candidate gene for attention-deficit hyperactivity disorder (ADHD). Noradrenergic systems are critical to higher brain functions such as attention and executive function, which are defective in ADHD. The clinical efficacy of medications that target NET also supports its role in the etiology of ADHD. Here, we have applied a dense mapping strategy to capture all genetic variations within the NET gene in a large number of ADHD families (474 trios). As a result, we found association of the same alleles from two single-nucleotide polymorphisms (rs3785143 and rs11568324) previously identified in another large-scale ADHD genetic study (International Multisite ADHD Geneproject). Furthermore, the effect sizes were consistent across both studies. This is the first time that identical alleles of NET from different studies were implicated, and thus our report provides further evidence that the NET gene is involved in the etiology of ADHD.

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Section: Discussioncontrasting

confidence: 67%

Further evidence of association between two NET single-nucleotide polymorphisms with ADHD

et al. 2007

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“…Associations reported by the larger pharmacogenetic studies include genes encoding the serotonin transporter, 2 norepinephrine transporter, 3 serotonin receptor HTR2A, 4 brain-derived neurotrophic factor (BDNF), 5 glucocorticoid receptor 6 and glucocorticoid-receptor-associated co-chaperone FKBP5. 7 With the notable exception of the length polymorphism in the serotonin transporter gene promoter, 2 these associations have not yet been replicated.…”

Section: Introductionmentioning

confidence: 99%

Genetic predictors of response to antidepressants in the GENDEP project

et al. 2009

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The objective of the Genome-based Therapeutic Drugs for Depression study is to investigate the function of variations in genes encoding key proteins in serotonin, norepinephrine, neurotrophic and glucocorticoid signaling in determining the response to serotonin-reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1.1% of variance (P ¼ 0.0016). Variants in the norepinephrine transporter gene (SLC6A2) predicted response to nortriptyline, and variants in the glucocorticoid receptor gene (NR3C1) predicted response to both antidepressants. Two HTR2A markers remained significant after hypothesis-wide correction for multiple testing. A false discovery rate of 0.106 for the three strongest associations indicated that the multiple findings are unlikely to be false positives. The pattern of associations indicated a degree of specificity with variants in genes encoding proteins in serotonin signaling influencing response to the serotonin-reuptake-inhibiting escitalopram, genes encoding proteins in norepinephrine signaling influencing response to the norepinephrine-reuptake-inhibiting nortriptyline and a common pathway gene influencing response to both antidepressants. The single marker associations explained only a small proportion of variance in response to antidepressants, indicating a need for a multivariate approach to prediction.

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“…Two functional polymorphisms in this gene, STin2 and the 5-HTTLPR (serotonin transporterlinked polymorphic region), have been associated with response to SSRIs. [10][11][12][13][14] Of particular interest is the 5-HTTLPR, a variable number tandem repeat with two common allelic variants, known as 'short' or S and 'long' or L, respectively. A comprehensive meta-analysis, including over 1400 participants revealed a modest association of the short variant of the 5-HTTLPR with poor response and remission to antidepressants.…”

Section: Introductionmentioning

confidence: 99%

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

et al. 2010

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Monoamine Transporter Gene Polymorphisms and Antidepressant Response in Koreans With Late-Life Depression

Cited by 185 publications

References 52 publications

Further evidence of association between two NET single-nucleotide polymorphisms with ADHD

Further evidence of association between two NET single-nucleotide polymorphisms with ADHD

Genetic predictors of response to antidepressants in the GENDEP project

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

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