Background: Previous evidence has suggested that norepinephrine transporter (NET) gene (solute carrier family 6, member 2 [SLC6A2]) polymorphisms are involved in antidepressant response. Specifically, the polymorphism T-182C (rs2242446) located in the promoter region of SLC6A2 has been found to be associated with antidepressant response in multiple ethnic backgrounds. However, the results are inconsistent. Moreover, few studies have focused on how this T-182C polymorphism might regulate SLC6A2 promoter function. Methods: In this study, luciferase reporter assays were performed to examine the functional significance of the T-182C polymorphism. In addition, we performed a meta-analysis to explore whether this genetic variant is significantly involved in the antidepressant response. Results: We found that the -182(T) allele significantly increased promoter function compared to the C allele based on luciferase reporter assays. For the meta-analysis, six articles were identified that explored the relationship between the NET T-182C polymorphisms and antidepressant response. This study revealed no significant association between these polymorphisms and response to antidepressants (OR = 1.23, 95% CI = 0.77 - 1.97, p = 0.38 for T-182C). Conclusions: The T-182C polymorphism enhances promoter activity, but may not be associated with antidepressant response.
Keywords: antidepressant response; meta-analysis; norepinephrine transporter gene; promoter activity.