期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 32, 期 1, 页码 1-5出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2011.147
关键词
Ala147Thr; PBR28; polymorphism; radioligand binding; TSPO
资金
- GlaxoSmithKline
- Imperial College London
- MRC [G0900897] Funding Source: UKRI
- Medical Research Council [G0900897] Funding Source: researchfish
- National Institute for Health Research [CL-2011-21-002] Funding Source: researchfish
[(11)C] PBR28 binds the 18-kDa Translocator Protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of signal are confounded by large interindividual variability in binding affinity, which displays a trimodal distribution compatible with a codominant genetic trait. Here, we tested directly for an underlying genetic mechanism to explain this. Binding affinity of PBR28 was measured in platelets isolated from 41 human subjects and tested for association with polymorphisms in TSPO and genes encoding other proteins in the TSPO complex. Complete agreement was observed between the TSPO Ala147Thr genotype and PBR28 binding affinity phenotype (P value =3.1x10(-13)). The TSPO Ala147Thr polymorphism predicts PBR28 binding affinity in human platelets. As all second-generation TSPO PET radioligands tested hitherto display a trimodal distribution in binding affinity analogous to PBR28, testing for this polymorphism may allow quantitative interpretation of TSPO PET studies with these radioligands. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1-5; doi:10.1038/jcbfm.2011.147; published online 19 October 2011
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