Genetic Variations in the Interleukin-6 and Interleukin-8 Genes and the Interleukin-6 Receptor Gene in Delirium

Objective: The aim of this study was to investigate whether genetic polymorphisms in the interleukin-6 gene (IL6), the IL-6 receptor gene (IL6R), and the IL-8 gene (IL8) were associated with delirium in a population of acutely admitted older patients. Methods: This was a prospective cohort study in the Academic Medical Center in Amsterdam, running from April, 2003, through August, 2008. A total of 881 patients, aged 65 years and older, acutely admitted to the medical department or to the surgical department following hip fracture, were included in the study. Delirium was diagnosed by the Confusion Assessment Method. Two single-nucleotide polymorphisms (SNPs) in the IL6 gene, one in the IL6R gene, and one in the IL8 gene were genotyped. Results: Fifty percent of the 115 surgical patients and 34% of the 605 medical patients experienced delirium. Delirious patients were older (82.8 years vs. 77.6 years) and had more frequent pre-existing functional (64% vs. 36%) or cognitive impairment (83% vs. 26%) (p < 0.001). The determination of polymorphisms had success rates between 87% and 96%. Rs1800697 and rs1800797 in the IL6 gene, rs8192284 in the IL6R gene, and rs4073 in the IL8 gene were not associated with the development of delirium. Conclusion: Recent observations have indicated that IL-6 and IL-8 play a role in delirium in the elderly, but functional genetic variations in the IL6, IL6R, and IL8 genes were not associated with delirium. Still, the inflammatory hypothesis of delirium is gaining ground in the literature on the basis of recent animal research.