Serotonin Transporter Gene Polymorphisms and Sertraline Response in Major Depression Patients

Abstract

Major depression (MD) has a complex multifactorial etiology with genetic and environmental factors contributing to the disorder. As with all antidepressant treatments, there is variability in drug response due to heredity, generally focusing on genetic polymorphism of the drug-metabolizing transporter genes. The serotonin transporter (5-HTT) gene is a particularly important candidate for genetic involvement in MD disorders owing to its key role in the regulation of serotonergic transmission and is therefore considered to be an interesting candidate in the mechanism of antidepressant drugs. In this study, we have focused on the associations between genetic polymorphisms in two regions of the 5-HTT gene (5-HTTLPR and VNTR) related to sertraline responses. Our sample consisted of 64 unrelated Turkish subjects who strictly met DSM-IV and CGI scores. There was no significant difference between the frequency of the SS, LS, LL, 9/10, 10/10, 9/12, 10/12, and 12/12 genotypes and responses to sertraline. However, the number of patients can be increased and different drugs can be studied in order to find a specific pharmacogenetic relation.

Association between Serotonin Transporter-Linked Polymorphic Region and Escitalopram Antidepressant Treatment Response in Korean Patients with Major Depressive Disorder

“…However, a number of studies conducted on Caucasian-dominant groups did not show similar results, with the s allele being associated with better treatment response/remission [46,47], or with the insertion/deletion genotype having no effect on treatment [48,49]. Studies conducted on Asian patients have shown even more opposing results on which variant is the favorable one for antidepressant treatment [18,19,35].…”

Pharmacogenetics of antidepressant response

“…163 These findings are generally well replicated in studies involving white popu lations, 120,[164][165][166][167][168][169][170][171][172][173][174][175] although opposite or inconsistent findings have also been reported. [176][177][178][179][180] On the other hand, studies involving Asian populations usually report conflicting results: some studies reported that the short 5-HTTLPR allele was associated with better outcomes, [181][182][183][184] some found no effect of 5-HTTLPR genotype on treatment efficacy 121,185,186 and some reported that the long 5-HTTLPR allele was associated with better outcomes. 83,[187][188][189][190][191] Interestingly, Lotrich and colleagues 192 recently reported that paroxetine blood concentration was positively associated with HAM-D response in a sample of elderly patients, but this association was found to be significant only in carriers of the short allele.…”

Pharmacogenetics of antidepressant drugs: An update

“…Another polymorphism influencing SERT expression, described as 17bp VNTR polymorphism, was identified within intron 2 (STin2) [80]. Several studies reported an influence of STin2 on response to ADs, but other investigations were not able to repeat these findings [81][82][83][84][85]. Moreover, it was proposed that STin2 10/12 genotype may be associated with poorer antidepressant effect, especially in Asian populations [86].…”