Norepinephrine Transporter (SLC6A2) Polymorphisms and their Impact on SSRI/SNRI Treatment response in Indian Patients with Depressive Disorder: A preliminary study
S. Sinha, S. C. Sarangi, D. Sharma, B. N. Patra, S. Singh, R. SagarIntroduction
Treatment-resistant depression is a major concern, though there has been significant advancement in antidepressant therapy. The therapeutic outcome for patients with depressive disorder is achieving a treatment response with remission. Predictions based on genetic markers may have the potential to increase the treatment response through a personalised approach. Norepinephrine neurotransmission is a major pathophysiological concern.
Objectives
To investigate the association of single-nucleotide polymorphisms (SNPs) in the norepinephrine transporter (SLC6A2) as predictive pharmacogenetic biomarkers with antidepressant response in the Indian population, by comparing treatment responders and non-responders to SSRI/SNRI monotherapy.
Methods
Two hundred thirty-eight patients suffering from depressive disorder were selected and enrolled for this study. The patients were treated with SSRI/SNRI over a period of 3 months. Standardised questionnaires were used for assessment, including the severity of depression assessed by the Hamilton Depression Rating Scale (HDRS) and the Centre for Epidemiologic Studies Depression Scale (CES-D), social cognition assessment using SOCRATIS, and side effects evaluation with the UKU Side Effect Rating Scale. Genetic variations SLC6A2 with their SNPs (rs5569 and rs36029) were genotyped. The genetic data of the responders and non-responders were compared to evaluate the role of genetic variants in therapeutic outcome.
Results
Out of the total patients, 136 (57.14%) showed a positive treatment response, with 32 (23.52%) achieving complete remission. Analysis of SNP rs36029 (A/G) revealed no significant association with responder/non-responder or remitter/non-remitter groups, nor with the eight most common side effects, except memory loss, which showed a significant (p = 0.029). For SNP rs5529 (G/A/C), the wild-type allele (G) was predominant among responders (56 patients, 37.3%), while mutant alleles A (19 patients, 12%) and C (1 patient, 0.7%) were less common. In non-responder groups, the G allele was less frequent (34 patients, 12.5%), with higher prevalence of A (29 patients, 17.3%) and C (11 patients, 7.3%). These findings suggest that mutant alleles, especially C, may reduce treatment efficacy.
Notably, the NET rs5569 allele C has not been previously reported in the Indian population.
Image 1: Long description.