Extended Evaluation of Serotonin Transporter Gene Functional Polymorphisms in Subjects with Post-Stroke Depression

Objective: As an extension of our previous observation, relating a serotonin transporter gene-linked promoter region (5-HTTLPR) diallelic functional polymorphism (short [S] and long [L] alleles) to the risk of post-stroke major depression (PSD), this study investigated the role of 2 other functional polymorphisms of the serotonin transporter gene (5-HTT) in the same sample of subjects with PSD. Method: In a clinical sample of 26 patients with PSD and 25 unrelated nondepressed stroke patients of Caucasian descent, we examined the frequencies of a functional single nucleotide variant (A/G) within the promoter region (rs25531) and located in L (16-repeat) and S (14-repeat) alleles of 5-HTTLPR, and a variable number tandem repeat (VNTR) polymorphism in intron 2. Results: There were significant intergroup differences in the allelic frequencies of 5-HTTLPR/rs25531 (S A , L A , and L G ) ( P < 0.05) and in the combined frequencies of lower-expressing alleles (S A and L G ) and higher-expressing alleles (L A ) ( P < 0.025) between subjects with PSD and nondepressed stroke. However, the differences in the combined frequencies of lower-expressing (S A /S A , S A /L G , and L G /L G ), intermediate-expressing (S A /L A and L A /L G ), and higher-expressing (L A /L A ) genotypes of 5-HTTLPR were not significant. Further, no significant intergroup differences were found in the allelic and genotypic frequencies of the intron 2 VNTR. Conclusions: These findings strengthen the support for an association between PSD and lower-expressing alleles of 5-HTTLPR.