Genetic polymorphisms in the DRD2, DRD3, and SLC6A3 gene in elderly patients with delirium

Dopamine excess appears to be critical in the final common pathway of delirium. The aim of this study was to investigate whether genetic polymorphisms in three dopamine-related genes (the dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), and the dopamine transporter (SLC6A3) gene) were associated with delirium. Patients aged 65 years and older acutely admitted to the medical department or to the surgical department following hip fracture were included. Delirium was diagnosed by the Confusion Assessment Method. Sixteen single nucleotide polymorphisms (SNPs) and one variable number of tandem repeats in the SLC6A3 gene, nine SNPs in the DRD2 gene, and six SNPs in the DRD3 gene were genotyped. Fifty percent of the 115 surgical patients and 34% of the 605 medical patients experienced delirium. Delirious patients were older and had more frequently pre-existing functional and cognitive impairment (P < 0.001). After correction for multiple testing, one SNP in the SLC6A3 gene (rs393795) was associated with reduced risk of delirium (P = 0.032). Adjusted for age, cognitive impairment, and functional impairment, three SNPs in the DRD2 gene and seven SNPs in the SLC6A3 gene were associated with delirium; none of these associations was significant after correction for multiple testing. Variations in the SLC6A3 gene and possibly the DRD2 gene were associated with delirium. Although validation of these results is needed our results support a role for the dopamine transporter and dopamine receptor 2 in the pathogenesis of delirium.