Genetic screening for mutations in the Nrdp1 gene in Parkinson disease patients in a Chinese population

Mo, Xiaoyun; Liu, Deyuan; Li, Wei; Hu, Zhengmao; Hu, Yiqiao; Li, Jingzhi; Guo, Jifeng; Tang, Beisha; Zhang, Zhuohua; Bai, Yi; Xia, Kun

doi:10.1016/j.parkreldis.2009.09.001

« Previous Next »Parkinsonism & Related Disorders
Volume 16, Issue 3 , Pages 222-224, March 2010

Genetic screening for mutations in the Nrdp1 gene in Parkinson disease patients in a Chinese population☆

Xiaoyun Mo
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
- Experimental Center, The People’s Hospital of Guangxi Zhuang Autonomous Region, NanNing, Guangxi, China
- These authors contributed equally to the study.
Deyuan Liu
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
- These authors contributed equally to the study.
Wei Li
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
Zhengmao Hu
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
Yiqiao Hu
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
Jingzhi Li
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
Jifeng Guo
- Department of Neurology, Xiangya Hospital, Central South University, ChangSha, Hunan, China
Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, ChangSha, Hunan, China
Zhuohua Zhang
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
Yi Bai
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
- Graduate school of Central South University, Central South University, ChangSha, Hunan, China
- Corresponding authors at: State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, China. Tel.: +86 731 84805357.
Kun Xia
- State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, Hunan 410078, China
- School of Biological Science and Technology, Central South University, ChangSha, Hunan, China
- Corresponding authors at: State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, China. Tel.: +86 731 84805357.

Received 2 April 2009; received in revised form 31 August 2009; accepted 2 September 2009.

Abstract

Strong evidence has shown that a defect in the Parkin gene is known to be a common, genetic cause of Parkinson disease (PD). The E3 ubiquitin ligase Nrdp1 is shown to interact with the N terminal of Parkin (the first 76 amino acids) and catalyze degradation of Parkin via the ubiquitin–proteasome pathway, suggesting that Nrdp1 may be involved in the development of PD via the regulation of Parkin, We believe we are the first to have screened PD patients for mutations in the Nrdp1 gene to determine the association between these variants and PD. By direct sequencing, we analysed the entire coding regions and 5′ UTR of Nrdp1 in 209 Chinese PD patients and 302 unrelated healthy individuals. No variant was detected in the coding regions (exons 3–7); only 2 variants (c.−206 T > A and c.−208–8 A > G) were identified in the 5′ UTR (exon 2) and intron 1. Furthermore, a study of the allelic and genotypic association between patients and controls showed no significant association between the c.−206 T > A polymorphism and PD; c.−208–8 A > G was identified in one PD patient and not in controls. Our data do not support the hypothesis of a major role for the Nrdp1 gene in PD development in the Chinese population.

Keywords: Parkinson disease, Parkin, Nrdp1, Mutation screening