The association of the dopamine transporter gene and the dopamine receptor 2 gene with delirium, a meta-analysis.
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.
van Munster
Barbara C
BC
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.
de Rooij
Sophia E J A
SEJA
Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Yazdanpanah
Mojgan
M
Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
Tienari
Pentti J
PJ
Department of Neurology, Helsinki University Central Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
Pitkälä
Kaisu H
KH
Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
Osse
Robert J
RJ
Department of Psychiatry, Erasmus MC, Rotterdam, the Netherlands.
Adamis
Dimitrios
D
Psychiatry, Research and Academic Institute of Athens, Athens, Greece.
Smit
Orla
O
Department of Internal Medicine, VU Medical Center, Amsterdam, the Netherlands.
van der Steen
Marijke S
MS
Intensive Care, Gelderse Vallei Hospital, Ede, the Netherlands.
van Houten
Miriam
M
Department of Geriatrics, Parnassia, Den Haag, the Netherlands.
Rahkonen
Terhi
T
Department of Geriatrics, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland.
Sulkava
Raimo
R
Department of Geriatrics, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland.
Laurila
Jouko V
JV
Helsinki University Central Hospital, Clinics of General Internal Medicine and Geriatrics, Helsinki, Finland.
Strandberg
Timo E
TE
Oulu University Hospital, Unit of General Practice, Oulu, Finland.
Tulen
Joke H M
JHM
Department of Psychiatry, Erasmus MC, Rotterdam, the Netherlands.
Zwang
Louwerens
L
Department of Clinical Chemistry, Erasmus MC, Rotterdam, the Netherlands.
MacDonald
Alastair J D
AJD
Elderly Care Unit, St Thomas' Hospital, Westminster, London, UK.
Treloar
Adrian
A
Memorial Hospital, Shooters Hill, London, UK.
Sijbrands
Eric J G
EJG
Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
Zwinderman
Aeilko H
AH
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Korevaar
Johanna C
JC
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
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*
D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human