The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms

Depress Anxiety. 2010 Mar;27(3):260-9. doi: 10.1002/da.20660.

Abstract

Background: We compare the genotype distribution for the serotonin transporter polymorphism (5-HTTLPR) in a sample of older Taiwanese adults with samples of various racial and ethnic groups collected in other studies. We also explore interactions among sex, stressors, and 5-HTTLPR genotype on depressive symptoms in our sample.

Methods: Using a nationally representative sample of 984 Taiwanese aged 53 and older, we model depressive symptoms as a function of 5-HTTLPR genotype and two classes of stressors: lifetime trauma and recent major life events. We test two- and three-way interactions among stressors, 5-HTTLPR, and sex.

Results: This sample exhibits higher frequency of S/S and lower frequency of L/L genotype than Western samples, but the distribution is comparable to those in East Asian populations. Nearly 9% carry an allele (XL) that has rarely been reported in the literature. Although the gene-environment (GxE) interaction with recent major life events is not significant, our results suggest that trauma has a worse effect on depressive symptoms for those with S/S or S/L genotype than for those who do not carry the S allele (P<0.05). We find no evidence that this GxE interaction varies by sex.

Conclusions: Previous studies of this GxE interaction have been inconclusive, perhaps because interactions between genotype and stressful events are more prominent under extreme stressors. Our findings underscore the need to move beyond a bi-allelic parameterization of the 5-HTTLPR polymorphism and raise questions about why East Asian populations exhibit low rates of depression despite a high frequency of the S allele.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles*
  • Depressive Disorder / ethnology
  • Depressive Disorder / genetics*
  • Depressive Disorder / psychology
  • Female
  • Genetic Variation / genetics*
  • Genotype
  • Humans
  • Life Change Events
  • Male
  • Middle Aged
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Taiwan / epidemiology

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins