Association between major depressive disorder and a functional polymorphism of the 5-hydroxytryptamine (serotonin) transporter gene

A meta-analysis

Chikako Kiyohara, Kouichi Yoshimasu

Research output: Contribution to journalReview article

58 Citations (Scopus)

Abstract

Objectives A functional polymorphism in the promoter region of the 5-hydroxytryptamine (serotonin) transporter (5-HTT) gene, termed 5-HTTLPR, alters transcription of the 5-HTT gene. The short variation (S allele) produces less transcriptional efficiency of serotonin, which can partly account for psychiatric disorders. Despite strong biological plausibility, the relationship between 5-HTTLPR and the risk of major depressive disorder (MDD) is unclear. To elucidate the relationship, we applied meta-analysis techniques to molecular studies of 5-HTTLPR and MDD. Methods A total of 22 articles were identified from MEDLINE through March 2008, using the search keywords 'depression,' '5-HTTLPR', and 'polymorphism.' The authors assessed the evidence of genotypic association using STATA Version 8.2. Results Summary frequencies of the S allele of 5-HTTLPR among Caucasians and Asians based on the random effects model were 42.1% [95% confidence interval (CI) = 40.5-43.6] and 76.8% (95% CI= 73.9-79.7), respectively. The distribution of the S allele was significantly different between Asians and Caucasians (P < 0.001). The SS genotype was significantly associated with an increased risk of MDD among Caucasian populations (odds ratio = 1.41, 95% CI= 1.15-1.72), although there was no significant association among Asians. Conclusion Although the summary risk for developing MDD in individuals with the 'at-risk' SS genotype of 5-HTTLPR may be small, MDD is such a common disease that even a small increase in risk translates to a large number of excess MDD cases in the population. Thus, 5-HTT may be a candidate MDD susceptibility gene.

Original languageEnglish
Pages (from-to)49-58
Number of pages10
JournalPsychiatric Genetics
Volume20
Issue number2
DOIs
Publication statusPublished - Apr 1 2010

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Serotonin Plasma Membrane Transport Proteins
Major Depressive Disorder
Meta-Analysis
Serotonin
Genes
Confidence Intervals
Alleles
Genotype
Genetic Promoter Regions
Gene Frequency
MEDLINE
Population
Psychiatry
Odds Ratio
Depression

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Association between major depressive disorder and a functional polymorphism of the 5-hydroxytryptamine (serotonin) transporter gene : A meta-analysis. / Kiyohara, Chikako; Yoshimasu, Kouichi.

In: Psychiatric Genetics, Vol. 20, No. 2, 01.04.2010, p. 49-58.

Research output: Contribution to journalReview article

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title = "Association between major depressive disorder and a functional polymorphism of the 5-hydroxytryptamine (serotonin) transporter gene: A meta-analysis",
abstract = "Objectives A functional polymorphism in the promoter region of the 5-hydroxytryptamine (serotonin) transporter (5-HTT) gene, termed 5-HTTLPR, alters transcription of the 5-HTT gene. The short variation (S allele) produces less transcriptional efficiency of serotonin, which can partly account for psychiatric disorders. Despite strong biological plausibility, the relationship between 5-HTTLPR and the risk of major depressive disorder (MDD) is unclear. To elucidate the relationship, we applied meta-analysis techniques to molecular studies of 5-HTTLPR and MDD. Methods A total of 22 articles were identified from MEDLINE through March 2008, using the search keywords 'depression,' '5-HTTLPR', and 'polymorphism.' The authors assessed the evidence of genotypic association using STATA Version 8.2. Results Summary frequencies of the S allele of 5-HTTLPR among Caucasians and Asians based on the random effects model were 42.1{\%} [95{\%} confidence interval (CI) = 40.5-43.6] and 76.8{\%} (95{\%} CI= 73.9-79.7), respectively. The distribution of the S allele was significantly different between Asians and Caucasians (P < 0.001). The SS genotype was significantly associated with an increased risk of MDD among Caucasian populations (odds ratio = 1.41, 95{\%} CI= 1.15-1.72), although there was no significant association among Asians. Conclusion Although the summary risk for developing MDD in individuals with the 'at-risk' SS genotype of 5-HTTLPR may be small, MDD is such a common disease that even a small increase in risk translates to a large number of excess MDD cases in the population. Thus, 5-HTT may be a candidate MDD susceptibility gene.",
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N2 - Objectives A functional polymorphism in the promoter region of the 5-hydroxytryptamine (serotonin) transporter (5-HTT) gene, termed 5-HTTLPR, alters transcription of the 5-HTT gene. The short variation (S allele) produces less transcriptional efficiency of serotonin, which can partly account for psychiatric disorders. Despite strong biological plausibility, the relationship between 5-HTTLPR and the risk of major depressive disorder (MDD) is unclear. To elucidate the relationship, we applied meta-analysis techniques to molecular studies of 5-HTTLPR and MDD. Methods A total of 22 articles were identified from MEDLINE through March 2008, using the search keywords 'depression,' '5-HTTLPR', and 'polymorphism.' The authors assessed the evidence of genotypic association using STATA Version 8.2. Results Summary frequencies of the S allele of 5-HTTLPR among Caucasians and Asians based on the random effects model were 42.1% [95% confidence interval (CI) = 40.5-43.6] and 76.8% (95% CI= 73.9-79.7), respectively. The distribution of the S allele was significantly different between Asians and Caucasians (P < 0.001). The SS genotype was significantly associated with an increased risk of MDD among Caucasian populations (odds ratio = 1.41, 95% CI= 1.15-1.72), although there was no significant association among Asians. Conclusion Although the summary risk for developing MDD in individuals with the 'at-risk' SS genotype of 5-HTTLPR may be small, MDD is such a common disease that even a small increase in risk translates to a large number of excess MDD cases in the population. Thus, 5-HTT may be a candidate MDD susceptibility gene.

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