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.


METHODS
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 (SA, LA, and LG) (P < 0.05) and in the combined frequencies of lower-expressing alleles (SA and LG) and higher-expressing alleles (LA) (P < 0.025) between subjects with PSD and nondepressed stroke. However, the differences in the combined frequencies of lower-expressing (SA/SA, SA/LG, and LG/LG), intermediate-expressing (SA/LA and LA/LG), and higher-expressing (LA/LA) 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.
Ramasubbu
Rajamannar
R
Department of Psychiatry and Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, Alberta. rramasub@ucalgary.ca
Tobias
Rose
R
Bech-Hansen
N Torben
NT
D003865:Major Depressive Disorder / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D047668:Inteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D020521:Stroke / Q000523:psychology*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins