Background: The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been proposed as a predictor of antidepressant response. Insertion or deletion of a 44bp long region gives rise to short 'S' and long 'L' forms of the promoter region, the 'S' form being associated with reduced serotonin transporter expression. Methods: A systematic review and meta-analysis was performed to clarify the effect of 5-HTTLPR on antidepressant response and remission rates. Data were obtained from 28 studies with 5408 participants. Three genotype comparisons were tested - SS versus (SL or LL), (SS or SL) versus LL, and SS versus LL. Results: There was no statistically significant effect on antidepressant response. Compared to L carriers, there was an apparent effect of the SS genotype on remission rate (RR 0.88; 95% CI 0.79 to 0.98; p=0.02). However, after trim and fill correction for missing data, the effect disappeared (RR 0.92; 95% CI 0.81 to 1.05; p=0.23) indicating that the initial significant effect was likely the result of publication bias. No significant effect on remission rate was seen for SS versus LL and SS/SL versus LL. Substantial unexplained heterogeneity of effect sizes was observed between studies, pointing to additional interacting factors contributing to an association in some cases. Conclusions: The 5-HTTLPR biallelic short/long polymorphism by itself does not appear to usefully predict antidepressant response
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