Polymorphic Ala-allele carriers at residue 1170 of HER2 associated with Parkinson's disease

Abstract Objective HER2, a receptor tyrosine kinase, was originally identified based on its role in cancer research. The protein has subsequently received attention for its role in nerve injury and neurodevelopment. We investigated the polymorphic association of HER2 variants at amino acid residues...

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Bibliographic Details
Published in:Journal of the neurological sciences 2013-02, Vol.325 (1), p.115-119
Main Authors: Wang, Vinchi, Chuang, Tzu-Chao, Kao, Ming-Ching, Shan, Din-E, Soong, Bing-Wen, Shieh, Tzong-Ming
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Ala carrier
Alanine - genetics
Alleles
Amino acids
Biological and medical sciences
Cell Survival - genetics
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dopamine - physiology
Female
HER2
Heterozygote
Humans
Male
Medical sciences
Middle Aged
Neurology
Parkinson Disease - diagnosis
Parkinson Disease - genetics
Parkinson Disease - pathology
Parkinson's disease
Polymorphism
Polymorphism, Genetic - genetics
Receptor, ErbB-2 - genetics
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Summary:Abstract Objective HER2, a receptor tyrosine kinase, was originally identified based on its role in cancer research. The protein has subsequently received attention for its role in nerve injury and neurodevelopment. We investigated the polymorphic association of HER2 variants at amino acid residues 655 and 1170 with Parkinson's disease (PD), a neurodegenerative disorder. Design and methods Polymerase chain reaction (PCR) was used to amplify DNA samples from PD patients and control subjects. The resulting PCR fragments, which spanned HER2 residues 655 and 1170, were analyzed by restriction fragment length polymorphism and/or direct nucleotide sequencing. Results The genetic distribution at residue 655 in PD patients did not differ from that in controls. However, homozygosity for genes encoding Pro at residue 1170 (Pro/Pro) occurred at a significantly lower rate among PD subjects. In other words, Ala-allele carries higher frequency in PD, especially among female PD subjects. Conclusion Different signals or potency of the kinase activities resulting from the Ala1170Pro allele of HER2 may be associated with vulnerability to stress on dopaminergic neurons in PD.
ISSN:0022-510X
1878-5883
DOI:10.1016/j.jns.2012.12.017