5-HTTLPR-rs25531 and Antidepressant Treatment Outcomes in Korean Patients with Major Depression

Abstract

Introduction Despite the ethnic differences in 5-HTTLPR (S allele relates to better antidepressant response in Korean and Japanese people, while L allele with better response in Caucasians), it is unclear whether 5-HTTLPR and its high expression locus rs25531 are interactively associated with antidepressant treatment outcome. We investigated the individual and interaction effects of these polymorphisms on antidepressant treatment outcomes in the Korean population. Methods A total of 464 Korean subjects with major depressive disorder completed 6 weeks of antidepressant monotherapy. Venous blood was extracted for genotyping 5-HTTLPR and rs25531 by polymerase chain reaction and DNA sequencing. We used logistic regression analyses to verify the main and interaction effects of 5-HTTLPR and rs25531 on response and remission after antidepressant treatment. Results After adjusting for covariates, the SS genotype of 5-HTTLPR was significantly associated with better treatment outcomes (p<0.001, odds ratio [OR] [95% confidence interval (CI)]=2.435 [1.551, 3.823] in response; p<0.001, OR [95% CI]=2.912 [1.730, 4.903] in remission), while G-containing genotype (AG+GG) of rs25531 was only associated with remission (p=0.034, OR [95% CI]=2.104 [1.058, 4.181]). The interaction effect of 5-HTTLPR and rs25531 on response and remission was insignificant (all p>0.05). Discussion Our findings suggest variations in allelic frequency and functionality of 5-HTTLPR and rs25531 among the different ethnicities. We found a minor advantage of rs25531 in achieving remission. However, there was no interaction effect with 5-HTTLPR.

SLC6A4 DNA Methylation Levels and Serum Kynurenine/Tryptophan Ratio in Eating Disorders: A Possible Link with Psychopathological Traits?

“…SERT is encoded by a gene (also known as the solute carrier family 6 member 4, SLC6A4 ) located on chromosome 17q11.2 [ 22 ]. Genetic variants within the promoter of this gene (i.e., rs25531 and rs25532) along with variable number tandem repeat (VNTR) polymorphisms in the promoter and intron 2 regions (5HTTLPR and STin2) modulate its transcriptional activity [ 23 ], influencing emotional, endocrine, and personality characteristics as well as vulnerability to a broad range of psychiatric disorders [ 24 , 25 , 26 , 27 ]. In this scenario, in vivo study demonstrated that transgenic mice overexpressing SLC6A4 are lighter and shorter than controls [ 28 ]; on the other hand, Slc6a4 knockout mice develop late-onset obesity, hepatic steatosis, glucose intolerance, and insulin resistance [ 29 ].…”

The Impact Of The Serotonin Transporter Gene Promoter DNA Methylation And Parenting Styles On Anorexia Nervosa

“…Serotonin Transporter Linked-Polymorphic Region (5-HTTLPR), located at the promoter region of the SLC6A4 gene, is one of the most investigated polymorphisms [16], which was discovered to affect the transcriptional activity of serotonin and regulate its expression [17]. There is some evidence that the 5-HTTLPR genotype affects vulnerability to a broad range of psychiatric disorders including depression [18], panic disorder (PD) [19], post-traumatic stress disorder (PTSD) [20], and so forth. While few studies have been performed in ED patients.…”

The Impact of the Serotonin Transporter Gene Promoter DNA Methylation on Anorexia Nervosa：A Preliminary Longitudinal Study

“…Serotonin Transporter Linked-Polymorphic Region (5-HTTLPR), located at the promoter region of the SLC6A4 gene, is one of the most investigated polymorphisms [14], which was discovered to impact the transcriptional activity of serotonin and regulate its expression [15]. There is some evidence that the 5-HTTLPR genotype affects vulnerability to a broad range of mental disorders including depression [16], panic disorder (PD) [17], post-traumatic stress disorder (PTSD) [18], and so forth. However, scarce studies have been performed in ED patients and longitudinal studies in AN have not yet been investigated.…”