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Glucocorticoid receptor haplotype is associated with a decreased risk of delirium in the elderly
Author(s) -
Manenschijn L.,
van Rossum E.F.C.,
Jetten A.M.,
de Rooij S.E.,
van Munster B.C.
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31165
Subject(s) - delirium , haplotype , glucocorticoid receptor , medicine , glucocorticoid , pathogenesis , allele , single nucleotide polymorphism , psychiatry , genotype , biology , gene , genetics
Delirium is the most common mental disorder at older age in hospitals after acute admission. The pathogenesis of delirium is largely unknown. Hyperactivity of the hypothalamic‐pituitary‐adrenal axis, leading to increased cortisol levels, has been suggested to play a role in the development of delirium. The effects of cortisol, the most important glucocorticoid (GC) in humans, are mainly mediated by the GC receptor (GR). Several polymorphisms in the GR gene that alter the GC sensitivity are known. The aim of this study was to study the role of these GR polymorphisms in delirium in elderly patients. Patients aged 65 years and older admitted to the medical department or scheduled for hip surgery were included. Delirium was diagnosed using the Confusion Assessment Method. Five single nucleotide polymorphisms in the GC receptor gene were genotyped and haplotypes were constructed. Delirium was associated with impaired cognitive ( P < 0.001) and functional function ( P < 0.001), as well as with older age ( P < 0.001). Homozygous carriers of haplotype 4, characterized by the presence of the Bcl I and TthIII I minor alleles, had a 92% decreased risk of developing delirium ( P = 0.02), independent of age, cognitive, and functional state. Homozygous carriage of the Bcl I‐ TthIII I haplotype of the GR gene is related to a reduced risk of developing delirium. This suggests that altered GC signaling may be involved in the pathogenesis and development of delirium in the elderly. © 2011 Wiley‐Liss, Inc.