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  • [Ann Nucl Med.] No effect of Parkinson's disease-polygenic load on striatal density of dopaminergic neuron in healthy subjects

    부산대병원 / 박경준*, 이명준*, 김인주*

  • 출처
    Ann Nucl Med.
  • 등재일
    2021 Nov
  • 저널이슈번호
    35(11):1187-1192. doi: 10.1007/s12149-021-01657-w. Epub 2021 Jul 21.
  • 내용

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    Abstract
    Objective: There has been increasing evidence to support the role of genetic factors in Parkinson's disease (PD). 123I-FP-CIT single-photon emission computed tomography (SPECT) enables in vivo visualization of the striatal density of dopaminergic neuron.

    Methods: We investigated the association between PD-associated polygenic load and striatal density of dopaminergic neuron in healthy subjects. Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database. 123I-FP-CIT SPECT was performed for all subjects. Specific binding ratios (SBRs) were calculated from the ventral striatum, caudate nucleus, and putamen with reference to cerebellum. Singe nucleotide polymorphism (SNP) genotyping from the PPMI database was adopted in calculating genetic risk score (GRS). GRS was defined as the sum of the number of risk alleles weighted by log odds ratios for PD. We calculated three GRSs using three different sets of SNPs.

    Result: A total of 151 subjects were included in this study (101 males, 50 females). GRS1, GRS2 and GRS3 were significantly different with the highest scores of GRS1. Multiple regression was done to investigate whether striatal SBRs are influenced by GRSs after adjusting for age and sex. However, none of GRSs were associated with SBRs of the ventral striatum, caudate nucleus and putamen.

    Conclusion: PD risk SNPs weighted by odds ratio for PD were not associated with SBRs measured from SPECT in healthy subjects. Therefore, there is no effect of PD-associated polygenic load on striatal density of dopaminergic neuron in healthy subjects.

     

     

    Affiliations

    Kyoungjune Pak #  1 , Myung Jun Lee #  2 , Keunyoung Kim  3 , In Joo Kim #  4
    1 Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea. ilikechopin@me.com.
    2 Department of Neurology and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea. mslayer9@gmail.com.
    3 Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea.
    4 Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 49241, Republic of Korea. injkim@pusan.ac.kr.
    # Contributed equally.

  • 키워드
    Dopaminergic neurons; Neuroimaging; Parkinson’s disease; Single nucleotide polymorphism.
  • 연구소개
    Parkinson’s progression markers initiative (PPMI) database를 이용하여, Parkinson’s disease의 발병에 영향을 미치는 single nucleotide polymorphism (SNP)이 정상인의 dopaminergic neuron에도 영향을 미칠 수 있는지를 조사한 연구입니다. 151명의 정상인에서 Parkinson’s disease 발병 관련 40여개의 SNP을 조합하여, 여러가지 polygenic risk score 만들었고, 이는 정상인의 I-123 FP-CIT SPECT에서 관찰되는 dopaminergic neuron과는 관련이 없는 것으로 확인되었습니다.
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