title: The association of the dopamine transporter gene and the dopamine receptor 2 gene with delirium, a meta-analysis.
abstract: Delirium is the most common neuropsychiatric syndrome in elderly ill patients. Previously, associations between delirium and the dopamine transporter gene (solute carrier family 6, member 3 (SLC6A3)) and dopamine receptor 2 gene (DRD2) were found. The aim of this study was to validate whether markers of the SLC6A3 and DRD2 genes are were associated with delirium in independent populations. Six European populations collected DNA of older delirious patients. Associations were determined per population and results were combined in a meta-analysis. In total 820 medical inpatients, 185 cardiac surgery patients, 134 non-cardiac surgery patients and 502 population-based elderly subjects were included. Mean age was 82 years (SD 7.5 years), 598 (36%) were male, 665 (41%) had pre-existing cognitive impairment, and 558 (34%) experienced delirium. The SLC6A3 rs393795 homozygous AA genotype was more frequent in patients without delirium in all populations. The meta-analysis showed an Odds Ratio (OR) for delirium of 0.4 (95% confidence interval (C.I.) 0.2-0.6, P = 0.0003) for subjects with AA genotype compared to the AG and GG genotypes. SLC6A3 marker rs1042098 showed no association with delirium. In meta-analysis the DRD2 rs6276 homozygous GG genotype showed an OR of 0.8 for delirium (95% C.I. 0.6-1.1, P = 0.24). When subjects were stratified for cognitive status the rs6276 GG genotype showed ORs of 0.6 (95% C.I. 0.4-1.0, P = 0.06) and 0.8 (95% C.I. 0.5-1.5, P = 0.51) for delirium in patients with and without cognitive impairment, respectively. In independent cohorts, a variation in the SLC6A3 gene and possibly the DRD2 gene were found to protect for delirium.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: van Munster
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Sophia E J A
authors.initials: SEJA
authors.lastname: de Rooij
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Yazdanpanah
authors.affiliation: Department of Neurology, Helsinki University Central Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
authors.forename: Pentti J
authors.initials: PJ
authors.lastname: Tienari
authors.affiliation: Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
authors.forename: Kaisu H
authors.initials: KH
authors.lastname: Pitkälä
authors.affiliation: Department of Psychiatry, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Osse
authors.affiliation: Psychiatry, Research and Academic Institute of Athens, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Adamis
authors.affiliation: Department of Internal Medicine, VU Medical Center, Amsterdam, the Netherlands.
authors.forename: Orla
authors.initials: O
authors.lastname: Smit
authors.affiliation: Intensive Care, Gelderse Vallei Hospital, Ede, the Netherlands.
authors.forename: Marijke S
authors.initials: MS
authors.lastname: van der Steen
authors.affiliation: Department of Geriatrics, Parnassia, Den Haag, the Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: van Houten
authors.affiliation: Department of Geriatrics, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland.
authors.forename: Terhi
authors.initials: T
authors.lastname: Rahkonen
authors.affiliation: Department of Geriatrics, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland.
authors.forename: Raimo
authors.initials: R
authors.lastname: Sulkava
authors.affiliation: Helsinki University Central Hospital, Clinics of General Internal Medicine and Geriatrics, Helsinki, Finland.
authors.forename: Jouko V
authors.initials: JV
authors.lastname: Laurila
authors.affiliation: Oulu University Hospital, Unit of General Practice, Oulu, Finland.
authors.forename: Timo E
authors.initials: TE
authors.lastname: Strandberg
authors.affiliation: Department of Psychiatry, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Joke H M
authors.initials: JHM
authors.lastname: Tulen
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Louwerens
authors.initials: L
authors.lastname: Zwang
authors.affiliation: Elderly Care Unit, St Thomas' Hospital, Westminster, London, UK.
authors.forename: Alastair J D
authors.initials: AJD
authors.lastname: MacDonald
authors.affiliation: Memorial Hospital, Shooters Hill, London, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Treloar
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Eric J G
authors.initials: EJG
authors.lastname: Sijbrands
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Korevaar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003693:Delirium / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005060:Europe; D005260:Female; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human