Serotonin transporter gene (SLC6A4) polymorphisms are associated with response to fluoxetine in south Indian major depressive disorder patients.

Objective: Up to 30-40 % of the major depressive disorder patients do not respond sufficiently to antidepressant treatment. Genetic variations in the serotonin transporter gene have been implicated in modulating treatment response to selective serotonin reuptake inhibitors, and this association is influenced by ethnicity. We investigated the influence of serotonin transporter gene variants 5-HTTLPR and rs25531 in Indian population on fluoxetine response.

Methods: One hundred and two major depressive disorder patients were started on fluoxetine treatment and after 6 weeks, classified as responders (n = 56) and non-responders (n = 46) using Hamilton depression rating scale and genotyped. Fisher's exact test was used to compare genotype frequencies between responders and non-responders. One-way analysis of variance and student t test were used to compare the percentage reduction (week 0-6) in Hamilton depression rating scores between genotype and haplotype groups.

Results: We observed a significant association between LL genotype of 5-HTTLPR and fluoxetine treatment response (p = 0.0066, OR (95 %) = 4.0 (1.45-11.03)) but not with the functional groups of 5-HTTLPR -rs25531. However, there was a significant difference in percentage reduction in HAM-D scores (week 0-6) between 5-HTTLPR genotypes (LL vs. LS + SS, p = 0.0036; LL vs. LS, p = 0.0109) as well as the functionally grouped haplotypes of 5-HTTLPR -rs25531 (LALA carriers vs. non-carriers of LALA, p = 0.0118; LALA vs. LAS+ LALG, p = 0.0419).

Conclusions: The LL genotype and LALA haplotype of SLC6A4 are associated with favorable treatment response to fluoxetine in south Indian major depression patients.