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


CONCLUSION
The LL genotype and LALA haplotype of SLC6A4 are associated with favorable treatment response to fluoxetine in south Indian major depression patients.
['Manoharan|Aarthi|A|', 'Shewade|Deepak Gopal|DG|', 'Rajkumar|Ravi Philip|RP|', 'Adithan|Surendiran|S|']
D000328:Adult D018687:Antidepressive Agents, Second-Generation D003865:Depressive Disorder, Major D005260:Female D005473:Fluoxetine D005838:Genotype D006801:Humans D008297:Male D008875:Middle Aged D011110:Polymorphism, Genetic D050486:Serotonin Plasma Membrane Transport Proteins D017367:Serotonin Uptake Inhibitors D016896:Treatment Outcome D044465:Whites
SLC6A4 Response Fluoxetine Major depression