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GAPDH rs1136666 SNP indicates a high risk of Parkinson's disease
Zhang Ping1, Wu Xiaomu2, Xie Xufang2
1Department of Neurology, Jiangxi Provincial People's Hospital, No, 92 Aiguo Road, Donghu District, Nanchang, 330006, Jiangxi, China; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, Hubei, China.
Background:
Development of Parkinson's disease (PD) is attributed to both genetic and environmental factors. Furthermore,GAPDH may play a key role in the development of neurodegenerative disease. Examination of genetic polymorphism in patients with sporadic PD will help uncover the mechanisms of PD pathogenesis and provide new insights into the treatment of PD.
Methods And Results:
The SNaPshot method was applied to determine the gene sequences in 265 patients with idiopathic PD and 269 control cases (sex- and age-matched). The rs1136666 polymorphism of GAPDH was determined to be closely associated with PD. Subsequently, the CC genotype of the rs1136666 fragment was transfected into SH-SY5Y cells via a plasmid. The genetic expression of rs1136666 CC could induce SH-SY5Y cell injury and apoptosis via regulation of the oxidant-antioxidant and apoptosis-antiapoptosis balance. rs1136666 CC of the GAPDH had a pro-apoptotic effect similar to that of rotenone, and combination of the rs1136666 CC genetic variation and the rotenone neurotoxic effect could aggravate oxidative stress, cell injury, and apoptosis better than either single treatment alone.
Conclusion:
This study confirmed that the rs1136666 CC allele of theGAPDH increased the risk of PD, particularly in older male patients.