Dementia and Neurocognitive Disorders (대한치매학회지)

Korean Dementia Association (대한치매학회)
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Translocator Protein (18 kDa) Polymorphism (rs6971) in the Korean Population

  • Hyon Lee (Department of Neurology, Gil Medical Center, Gachon University College of Medicine) ;
  • Young Noh (Department of Neurology, Gil Medical Center, Gachon University College of Medicine) ;
  • Woo Ram Kim (Neuroscience Research Institute, Gachon University) ;
  • Ha-Eun Seo (Neuroscience Research Institute, Gachon University) ;
  • Hyeon-Mi Park (Department of Neurology, Gil Medical Center, Gachon University College of Medicine)
  • Received : 2022.04.19
  • Accepted : 2022.04.25
  • Published : 2022.04.30
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Abstract

Background and Purpose: The expression of the 18-kDA mitochondrial translocator protein (TSPO) in the brain is an attractive target to study neuroinflammation. However, the binding properties of TSPO ligands are reportedly dependent on genetic polymorphism of the TSPO gene (rs6971). The objective of this study is to investigate the rs6971 gene polymorphism in the Korean population. Methods: We performed genetic testing on 109 subjects including patients with mild cognitive impairment, Alzheimer's disease (AD) dementia, non-AD dementia, and cognitively unimpaired participants. Magnetic resonance imaging scans and detailed neuropsychological tests were also performed, and 29 participants underwent 18F-DPA714 PET scans. Exon 4 of the TSPO gene containing the polymorphism rs6971 (Ala or Thr at position 147) was polymerase chain reaction amplified and sequenced using the Sanger method. The identified rs6971 genotype codes (C/C, C/T, or T/T) of the TSPO protein generated high-, mixed-, or low-affinity binding phenotypes (HABs, MABs, and LABs), respectively. Results: We found that 96.3% of the study subjects were HAB (105 out of 109 subjects), and 3.7% of the subjects were MAB (4 out of 109 subjects). 18F-DPA-714 PET scans showed nonspecific binding to the thalamus and brainstem, and increased tracer uptake throughout the cortex in cognitively impaired patients. The participant with the MAB polymorphism had a higher DPA714 signal throughout the cortex. Conclusions: The majority of Koreans are HAB (aprox. 96%). Therefore, the polymorphism of the rs6971 gene would have a smaller impact on the availability of second-generation TSPO PET tracers.

Keywords

Acknowledgement

This study was supported by a grant of the Korea Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant No: HI14C1135).

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