Association of Nurr1 gene mutations with Parkinson's disease in the Han population living in the Hubei province of China

摘要

Nurr1 defects could in part underlie Parkinson's disease pathogenesis, and Nurr1 gene polymorphism has been found in Caucasian patients with Parkinson's disease. In this study, heteroduplex technology was applied to compare the DNA sequences of eight exons of Nurr1 among 200 sporadic Parkinson's disease patients and 200 healthy controls in the Han population in the Hubei province, China. One allele amplified from exon 3 of Nurr1 was polymorphic in five Parkinson's disease patients (2.5%, 5/200), and two individuals had a polymorphic allele amplified from exon 2 (1%, 2/200). The anomalous electrophoresis fragment in exon 3 of Nurr1 gene contained a 709C/A missense mutation, and a polymorphic single nucleotide polymorphism at 388G/A was identified in exon 2. Compared with the control group, the Nurr1 gene expression level in the Parkinson's disease group was decreased, and the Nurr1 gene expression levels in Parkinson's disease patients carrying the polymorphisms at exons 2 and 3 were significantly decreased. Our data indicate that the single nucleotide polymorphism 388G/A in exon 2 and the 709C/A missense mutation in exon 3 of the Nurr1 gene in the Chinese population might affect the pathogenesis of Parkinson's disease. Research Highlights Heteroduplex analysis was used to conduct gene screening of eight exons of Nurr1 gene among Parkinson's disease patients and controls.Missense mutations in exons 2 and 3 of the Nurr1 gene were found in Chinese patients with Parkinson's disease. Abbreviations DA, dopaminergic neurons; TH, tyrosine hydroxylase