Association of a dopamine beta-hydroxylase gene variant with depression in elderly women possibly reflecting noradrenergic dysfunction

J Affect Disord. 2008 Feb;106(1-2):169-72. doi: 10.1016/j.jad.2007.06.010. Epub 2007 Aug 14.

Abstract

Background: Depression has a multifactorial etiology which involves genetic factors and comorbid diseases.

Methods: A cross-sectional sample of 1371 elderly women (mean age=69.2 years) was examined. Detailed information on their health was obtained. Cognitive functions were assessed by the Short Blessed Test and the Animal Naming Task. A 19 bp insertion/deletion polymorphism in the dopamine beta-hydroxylase (DBH) gene, the apolipoprotein (APOE) epsilon2/epsilon3/epsilon4 variation and 5-HTTLPR in the serotonin transporter gene were genotyped.

Results: Depression was univariately associated with homozygosity for the DBH gene 19 bp deletion allele (odds ratio [OR]=1.96, 95% confidence intervals [95% CI]=1.17-3.29, p=0.01), family history of depression (OR=3.86, 95% CI=1.85-8.06, p=0.0003), a composite measure of cardiovascular diseases (OR=1.96, 95% CI=1.11-3.47, p=0.02), cognitive impairment assessed by the Short Blessed Test (OR=3.88, 95% CI=1.29-11.64, p=0.02) and performance on the Animal Naming Task (OR=0.74, 95% CI=0.59-0.93, p=0.01). The strength of the association of DBH genotype with depression essentially remained unchanged after correction for other variables in a multivariate model. This association may reflect noradrenaline dysfunction in the brain.

MeSH terms

  • Aged
  • Alleles
  • Apolipoproteins E / genetics
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics
  • Comorbidity
  • Cross-Sectional Studies
  • Dementia / diagnosis
  • Dementia / epidemiology
  • Dementia / genetics
  • Denmark
  • Depressive Disorder / diagnosis
  • Depressive Disorder / epidemiology
  • Depressive Disorder / genetics*
  • Dopamine beta-Hydroxylase / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Homozygote
  • Humans
  • INDEL Mutation / genetics*
  • Middle Aged
  • Norepinephrine / physiology*
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics
  • Prospective Studies
  • Risk Factors
  • Serotonin Plasma Membrane Transport Proteins / genetics

Substances

  • Apolipoproteins E
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Dopamine beta-Hydroxylase
  • Norepinephrine