Serotonin Transporter (5-HTT) Gene Polymorphisms and Susceptibility to Epilepsy: A Meta-Analysis and Meta-Regression

Aims: Serotonin transporter (5-HTT) plays a central role in the regulation of serotonin (5-hydroxytryptamine [5-HT]) synaptic function. Disturbances in 5-HT transmission are the most frequently reported neurobiological substrates of suicidal behavior. Emerging evidence has shown that the common polymorphisms in the 5-HTT gene may contribute to the risk of epilepsy, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the associations between 5-HTT gene polymorphisms and susceptibility to epilepsy. Methods: A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before June 1st, 2013. Crude odds ratios with 95% confidence intervals were calculated. Results: Seven studies were assessed with a total 1303 epilepsy patients and 1288 healthy controls. The meta-analysis results indicated that there was no significant relationship between 5-HTT gene polymorphisms and an increased risk of epilepsy. Further subgroup analysis based on ethnicity also found no significant association between 5-HTT gene polymorphisms and epilepsy risk among both Caucasian and Asian populations. In addition, there was also no significant association between 5-HTT gene polymorphisms and the risk of psychiatric comorbidity in patients with epilepsy. Conclusion: In conclusion, the current meta-analysis indicates that 5-HTT gene polymorphisms might not be the primary determinants of epilepsy susceptibility. 5-HTT genes might be expected to interact with other genes in different signaling pathways to initiate and promote the epileptogenic process.