Journal of Molecular Neuroscience

, Volume 59, Issue 3, pp 343–350 | Cite as

SEPT14 Is Associated with a Reduced Risk for Parkinson’s Disease and Expressed in Human Brain

  • Liron Rozenkrantz
  • Ziv Gan-Or
  • Mali Gana-Weisz
  • Anat Mirelman
  • Nir Giladi
  • Anat Bar-Shira
  • Avi Orr-Urtreger
Article

Abstract

Genes involved in cytoskeletal stability and trafficking, such as MAPT and SNCA, are important risk factors for Parkinson’s disease (PD). Two members of the cytoskeletal Septin family, SEPT4 and SEPT5, were implicated in PD pathobiology. We aimed to determine whether Septin genes are associated with Parkinson’s disease. To this end, six SNPs located in four different Septin loci were analyzed in 720 PD patients and 740 controls, all of Ashkenazi–Jewish origin. In addition, SEPT14 was sequenced and its expression was determined in different human tissues. Our results revealed that two SNPs in the SEPT14 locus, rs11981883 and rs10241628, were associated with a reduced risk for PD (p = 0.02 and p = 0.005). A third SNP, rs77231105, was localized in the putative promoter of SEPT14 and was predicted to affect the binding of the transcription factor Nkx2.5. This SNP was also associated with a reduced risk for PD (OR = 0.28, p < 0.0007). The three SEPT14 SNPs defined a protective haplotype which significantly reduced the risk for PD by 4-fold (p = 0.002). SEPT14 was found to be expressed in the brain and in the Substantia Nigra. These results suggest that SEPT14 may have a protective role in Parkinson’s disease pathogenesis, yet more studies are necessary to validate these results.

Keywords

Parkinson’s disease Septin 14 SEPT14 Genetics 

Supplementary material

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ESM 1(DOCX 233 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Liron Rozenkrantz
    • 1
    • 2
  • Ziv Gan-Or
    • 1
    • 2
  • Mali Gana-Weisz
    • 1
  • Anat Mirelman
    • 3
  • Nir Giladi
    • 2
    • 3
  • Anat Bar-Shira
    • 1
  • Avi Orr-Urtreger
    • 1
    • 2
  1. 1.The Genetic InstituteTel-Aviv Sourasky Medical CenterTel AvivIsrael
  2. 2.Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael
  3. 3.Movement Disorders Unit, Parkinson Center, Department of NeurologyTel-Aviv Sourasky Medical CenterTel-AvivIsrael

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