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.
Subject(s)
Depressive Disorder/genetics , Dopamine beta-Hydroxylase/genetics , Genetic Predisposition to Disease/genetics , INDEL Mutation/genetics , Norepinephrine/physiology , Polymorphism, Genetic/genetics , 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 , Female , Follow-Up Studies , Genotype , Homozygote , Humans , Middle Aged , Promoter Regions, Genetic/genetics , Prospective Studies , Risk Factors , Serotonin Plasma Membrane Transport Proteins/geneticsABSTRACT
BACKGROUND: Genetic and environmental factors influence cognitive aging. The gene encoding dopamine beta-hydroxylase (DBH) could be one such factor since this hydroxylase converts dopamine to norepinephrine both of which are involved in cognition regulation. OBJECTIVE: To assess the effect of the 19bp insertion/deletion polymorphism in the 5' flank of the DBH gene on cognitive performance in elderly women relative to other factors of cognitive aging. METHODS: We examined a cross-sectional sample of 1371 postmenopausal women. Cognitive abilities were assessed by the 6-item orientation-memory-concentration test. The 19bp insertion/deletion polymorphism of the DBH gene was genotyped and apolipoprotein E (APOE) epsilon4 allele status was determined. In addition blood pressure, body fat mass and blood lipids were measured. Information was also obtained by personal interviews. Data were analyzed by regression analysis. RESULTS: Cognition was univariately associated with DBH genotype (p = 0.04). A univariate association of borderline significance was observed for APOE epsilon4 allele status (p = 0.07). Exclusion of women with severe cognition impairment did not alter the strength of the association with the DBH gene polymorphism markedly (p = 0.06) but obliterated the weak association between APOE epsilon4 allele status and cognition. The association of the DBH gene polymorphism with cognition persisted after adjustment for other variables (p = 0.03). CONCLUSIONS: The 19bp insertion/deletion polymorphism of the DBH gene influences cognition in elderly women and might have a stronger effect than APOE epsilon4 allele status on mild cognitive impairment. Both genetic polymorphisms had a significantly smaller impact on cognition than age, education, alcohol consumption and body fat measures.
