Bipolar Disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa Translocator Protein (TSPO).
TSPO mediated transport of cholesterol into the mitochondrion is a necessary step in steroid synthesis. The rs6971 polymorphism in the TSPO gene causes an amino acid substitution (Ala147Thr) within the transmembrane domain where the cholesterol-binding pocket is located, and has been shown to affect the steroidogenic pathway. We report a nominal association between this TSPO polymorphism and the diagnosis of Bipolar Disorder in both the genome-wide dataset of the Wellcome Trust Case-Control Consortium and the Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder group (OR=1.11, p=0.007; OR=1.10, p=0.011, respectively). We propose that the amino acid substitution affects hypothalamic-pituitary-adrenal (HPA) regulation, and hence may predispose to Bipolar Disorder. This supports the hypothesis that HPA dysregulation has a causal role in Bipolar Disorder, and is not just a consequence of the disease.
Division of Brain Sciences, Imperial College, London, United Kingdom; Imanova Centre for Imaging Sciences, Hammersmith Hospital Campus, London, United Kingdom. Electronic address: a.colasanti@imperial.ac.uk.
Alessandro
A
Colasanti
David R
DR
Owen
Detelina
D
Grozeva
Eugenii A
EA
Rabiner
Paul M
PM
Matthews
Nick
N
Craddock
Allan H
AH
Young
D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018079:Receptors, GABA / Q000235:genetics*
D018079:Receptors, GABA; C499229:TSPO protein, human
Bipolar Disorder; Cortisol; Genome-wide; HPA; Mitochondria; Neurosteroids; Polymorphism; Translocator Protein; WTCCC; rs6971