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Research paper
Polymorphisms of the serotonin transporter gene and post-stroke depression: a meta-analysis
  1. Kwok Kei Mak1,
  2. Wan Yee Kong2,
  3. Anselm Mak3,
  4. Vijay Kumar Sharma3,
  5. Roger C M Ho2
  1. 1Department of Community Medicine and School of Public Health, University of Hong Kong, Hong Kong
  2. 2Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  3. 3Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  1. Correspondence to Dr Roger C M Ho, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Level 9 NUHS Tower Block, 1E Kent Ridge Road, Singapore 119228; pcmrhcm{at}nus.edu.sg

Abstract

Background Polymorphisms of the gene encoding the serotonin transporter—specifically, length variation in the serotonin-transporter-linked polymorphic region (5-HTTLPR), a single-nucleotide polymorphism in the 5-HTTLPR (rs25531), and variable number of tandem repeats (VNTR) in the second intron 2 (STin2)—have been implicated in the development of post-stroke depression (PSD).

Objective To evaluate the association between polymorphisms of the serotonin transporter gene and PSD in the medical literature.

Methods Random-effects meta-analyses were conducted on cross-sectional, case–control and cohort studies examining relations between polymorphisms of the gene encoding the serotonin transporter and the risk of developing PSD.

Results Four studies comprising 260 stroke patients with PSD and 381 without were included. Our analyses showed a significant and positive association between the homozygous short variation (S) allele genotype of the 5-HTTLPR (SS) and PSD (random-effects pooled OR 2.05, 95% CI 1.41 to 2.98, z=3.79, p<0.001). Our analyses also showed a significant and negative association between the homozygous long variation (L) allele genotype of the 5-HTTLPR (LL) and PSD (random-effects OR 0.52, 95% CI 0.27 to 0.97, z=−2.07, p=0.039). No statistically significant association of PSD with heterozygous S and L allele genotype for 5-HTTLPR or other polymorphisms with rs25531 and STin2 VNTR was found. Heterogeneity and publication bias were not statistically significant. The major limitation of this meta-analysis is that we could not assess the interaction between stroke, environmental stress and PSD.

Conclusions The 5-HTTLPR SS genotype may be a risk factor for PSD. The 5-HTTLPR LL genotype showed a significant negative association with PSD. Further research to assess the sensitivity and specificity of predicting the risk of developing PSD by screening for the 5-HTTLPR genotype in stroke patients is required.

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