SEPT14 Is Associated with a Reduced Risk for Parkinson's Disease and Expressed in Human Brain.
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.
The Genetic Institute, Tel-Aviv Sourasky Medical Center, Weizmann 10, 64239, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, 39040, Tel-Aviv, Israel.
Liron
L
Rozenkrantz
The Genetic Institute, Tel-Aviv Sourasky Medical Center, Weizmann 10, 64239, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, 39040, Tel-Aviv, Israel.
Ziv
Z
Gan-Or
The Genetic Institute, Tel-Aviv Sourasky Medical Center, Weizmann 10, 64239, Tel Aviv, Israel.
Mali
M
Gana-Weisz
Movement Disorders Unit, Parkinson Center, Department of Neurology, Tel-Aviv Sourasky Medical Center, Weizmann 10, 64239, Tel-Aviv, Israel.
Anat
A
Mirelman
Sackler Faculty of Medicine, Tel-Aviv University, 39040, Tel-Aviv, Israel.|Movement Disorders Unit, Parkinson Center, Department of Neurology, Tel-Aviv Sourasky Medical Center, Weizmann 10, 64239, Tel-Aviv, Israel.
Nir
N
Giladi
The Genetic Institute, Tel-Aviv Sourasky Medical Center, Weizmann 10, 64239, Tel Aviv, Israel.
Anat
A
Bar-Shira
The Genetic Institute, Tel-Aviv Sourasky Medical Center, Weizmann 10, 64239, Tel Aviv, Israel. aviorr@tasmc.health.gov.il.|Sackler Faculty of Medicine, Tel-Aviv University, 39040, Tel-Aviv, Israel. aviorr@tasmc.health.gov.il.
Avi
A
Orr-Urtreger
D000368:Aged; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D058112:Septins / Q000235:genetics* / Q000378:metabolism
C527449:SEPTIN14 protein, human; D058112:Septins
Genetics; Parkinson’s disease; SEPT14; Septin 14