Human Genetics

, 124:89

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

Authors

  • Ikuko Mizuta
    • Division of Clinical Genetics, Department of Medical GeneticsOsaka University Graduate School of Medicine
    • Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
  • Tatsuhiko Tsunoda
    • Laboratory for Medical Informatics, SNP Research CenterThe Institute of Physical and Chemical Research (RIKEN)
  • Wataru Satake
    • Division of Clinical Genetics, Department of Medical GeneticsOsaka University Graduate School of Medicine
  • Yuko Nakabayashi
    • Division of Clinical Genetics, Department of Medical GeneticsOsaka University Graduate School of Medicine
    • Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
  • Masahiko Watanabe
    • Department of Neurology, Graduate School of Comprehensive Human SciencesUniversity of Tsukuba
  • Atsushi Takeda
    • Division of Neurology, Department of NeuroscienceTohoku University Graduate School of Medicine
  • Kazuko Hasegawa
    • Department of NeurologyNational Hospital Organization, Sagamihara National Hospital
  • Kenji Nakashima
    • Department of NeurologyTottori University Faculty of Medicine
  • Mitsutoshi Yamamoto
    • Department of NeurologyKagawa Prefectural Central Hospital
  • Nobutaka Hattori
    • Department of NeurologyJuntendo University School of Medicine
  • Miho Murata
    • Department of NeurologyMusashi Hospital, National Center of Neurology and Psychiatry
    • Division of Clinical Genetics, Department of Medical GeneticsOsaka University Graduate School of Medicine
    • Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
Original Investigation

DOI: 10.1007/s00439-008-0525-5

Cite this article as:
Mizuta, I., Tsunoda, T., Satake, W. et al. Hum Genet (2008) 124: 89. doi:10.1007/s00439-008-0525-5

Abstract

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.

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).

Copyright information

© Springer-Verlag 2008