Human Genetics

, 124:89 | Cite as

Calbindin 1, fibroblast growth factor 20, and α-synuclein in sporadic Parkinson’s disease

  • Ikuko Mizuta
  • Tatsuhiko Tsunoda
  • Wataru Satake
  • Yuko Nakabayashi
  • Masahiko Watanabe
  • Atsushi Takeda
  • Kazuko Hasegawa
  • Kenji Nakashima
  • Mitsutoshi Yamamoto
  • Nobutaka Hattori
  • Miho Murata
  • Tatsushi Toda
Original Investigation


Parkinson’s disease (PD), one of the most common human neurodegenerative disorders, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. Our recent case-control association study of 268 SNPs in 121 candidate genes identified α-synuclein (SNCA) as a susceptibility gene for sporadic PD (P = 1.7 × 10−11). We also replicated the association of fibroblast growth factor 20 (FGF20) with PD (P = 0.0089). To find other susceptibility genes, we added 34 SNPs to the previous screen. Of 302 SNPs in a total 137 genes, but excluding SNCA, SNPs in NDUFV2, FGF2, CALB1 and B2M showed significant association (P < 0.01; 882 cases and 938 control subjects). We replicated the association analysis for these SNPs in a second independent sample set (521 cases and 1,003 control subjects). One SNP, rs1805874 in calbindin 1 (CALB1), showed significance in both analyses (P = 7.1 × 10−5; recessive model). When the analysis was stratified relative to the SNCA genotype, the odds ratio of CALB1 tended to increase according to the number of protective alleles in SNCA. In contrast, FGF20 was significant only in the subgroup of SNCA homozygote of risk allele. CALB1 is a calcium-binding protein that widely is expressed in neurons. A relative sparing of CALB1-positive dopaminergic neurons is observed in PD brains, compared with CALB1-negative neurons. Our genetic analysis suggests that CALB1 is associated with PD independently of SNCA, and that FGF20 is associated with PD synergistically with SNCA.


Dopaminergic Neuron Recessive Model Pairwise Linkage Disequilibrium Analysis Single Linkage Disequilibrium Block Potential Combinational Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We are grateful to the PD patients who participated in this study. We also thank Chiyomi Ito, Satoko Suzuki, and Dr. Yoshio Momose for help in performing the study; Drs. Akira Oka, Hidetoshi Inoko, and Katsushi Tokunaga for control samples; and Dr. Jennifer Logan for editing the manuscript. This work was supported by a grant from Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST); by the twenty-first Century COE program and KAKENHI (17019044 and 19590990), both from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; and by the Grant-in-Aid for “the Research Committee for the Neurodegenerative Diseases” of the Research on Measures for Intractable Diseases and Research Grant (H19-Genome-Ippan-001), all from the Ministry of Health, Labor, and Welfare of Japan.

Supplementary material

439_2008_525_MOESM1_ESM.doc (42 kb)
Supplementary Table 1 Summary of the First Screen of 34 SNPs (DOC 67 kb).
439_2008_525_MOESM2_ESM.doc (76 kb)
Supplementary Table 2 Association Analysis of the 26 SNPs (DOC 76 kb).
439_2008_525_MOESM3_ESM.doc (36 kb)
Supplementary Table 3 Haplotype Association Analysis in CALB1 region (DOC 36 kb).
439_2008_525_MOESM4_ESM.doc (35 kb)
Supplementary Table 4 Information of SNPs tagged by rs1805874 and four neighboring SNPs (DOC 68 kb).
439_2008_525_Fig2_ESM.jpg (27 kb)
Distribution of SNPs tagged by PD-associated SNP rs1805874 and four closely neighboring ones showing no association (rs2074596, rs12549239, rs12171665, and rs12541465). The five tag SNPs are presented by vertical lines. The SNPs tagged by rs1805874 are shown in red. All the SNP IDs are listed in Supplementary Table 4 (JPEG 26 kb).


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ikuko Mizuta
    • 1
    • 2
  • Tatsuhiko Tsunoda
    • 3
  • Wataru Satake
    • 1
  • Yuko Nakabayashi
    • 1
    • 2
  • Masahiko Watanabe
    • 4
  • Atsushi Takeda
    • 5
  • Kazuko Hasegawa
    • 6
  • Kenji Nakashima
    • 7
  • Mitsutoshi Yamamoto
    • 8
  • Nobutaka Hattori
    • 9
  • Miho Murata
    • 10
  • Tatsushi Toda
    • 1
    • 2
  1. 1.Division of Clinical Genetics, Department of Medical GeneticsOsaka University Graduate School of MedicineSuitaJapan
  2. 2.Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology AgencySaitamaJapan
  3. 3.Laboratory for Medical Informatics, SNP Research CenterThe Institute of Physical and Chemical Research (RIKEN)YokohamaJapan
  4. 4.Department of Neurology, Graduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaJapan
  5. 5.Division of Neurology, Department of NeuroscienceTohoku University Graduate School of MedicineSendaiJapan
  6. 6.Department of NeurologyNational Hospital Organization, Sagamihara National HospitalSagamiharaJapan
  7. 7.Department of NeurologyTottori University Faculty of MedicineYonagoJapan
  8. 8.Department of NeurologyKagawa Prefectural Central HospitalTakamatsuJapan
  9. 9.Department of NeurologyJuntendo University School of MedicineTokyoJapan
  10. 10.Department of NeurologyMusashi Hospital, National Center of Neurology and PsychiatryKodairaJapan

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