Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy

In the last decade the serotonin transporter gene promoter polymorphism (5-HTTLPR) was likely the most studied genetic variant as predictor of antidepressant response. Nevertheless results are not consistent across studies and previous meta-analysis, since various factors seem to modulate its effect on antidepressant response.With the aim of clarifying this issue, we systematically reviewed literature, selecting 33 studies for an exploratory analysis without any a priori hypothesis. Then we analyzed separately 19 studies performed on Caucasians and 11 on Asians. We tested two phenotypes – remission and response rates – and three genotype comparisons – ll versus ls/ss, ss versus ll/ls and ll versus ss – using the Cochrane review manager. Evaluations were performed separately for SSRIs and mixed/other drugs. Possible clinical modulators were investigated.In the exploratory analysis, we found an association between l allele and l/l genotype and remission. When the analysis was split for ethnic group, in Caucasians we found an association between l allele and both response (OR = 1.58, C.I. 1.16–2.16, p = 0.004), and remission (OR = 1.53, C.I. 1.14–2.04, p = 0.004) in the SSRI group. Only a marginal association between l allele and remission (OR = 1.41, C.I. 1.02–1.95, p = 0.04) survived pooling together mixed antidepressant treatments. In Asians, a small effect of 5-HTTLPR on remission for mixed antidepressants was detected (OR = 2.10, C.I. 1.15–3.84, p = 0.02). Gender, age and age at onset modulated the association in Caucasians. Gender, age and depression severity at baseline modulated the association in Asians.In conclusion, in Caucasians 5-HTTLPR may be a predictor of antidepressant response and remission, while in Asians it does not appear to play a major role.

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