Abstract
Pathological mutations in the glucocerebrosidase gene (GBA) have been suggested to be associated with Parkinson’s disease (PD) in various ethnic populations. Most studies on Chinese PD patients have only screened the N370S and L444P mutations in the GBA gene. To investigate the GBA mutations in Chinese population, we performed complete sequencing of the GBA gene in 184 Chinese PD patients and 130 Chinese control individuals. As a result, we identified three novel and nine reported GBA mutations. The novel mutations include 5-bp deletion (c.334_338delCAGAA), L264I and L314V and the nine reported GBA mutations are R163Q, F213I, E326K, S364S, F347L, V375L, L444P, RecNciI and Q497R. The novel 5-bp deletion (CAGAA) produces a short truncated GBA protein of 142 amino acids, which loses major function domains of the 536 amino acids. Our data also reveals that the frequency of GBA mutations within this Chinese PD cohort was 8.7%, which is significantly higher than 1.54% observed in the Chinese control cohort (χ2=7.22, P=0.0072; odds ratio (OR)=6.095, 95% confidence interval of OR=1.546–24.030). The most common L444P mutation accounts 2.74%, which confer more genetic risk for PD in this Chinese population. In conclusion, novel and known GBA mutations were identified and were found to be associated to PD in this Chinese population.
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Acknowledgements
We thank all the participants from Canada and China. Funding was provided by the research grants from Research scholar Fund of Liaocheng People’s Hospital of Shandong province (NO. 2011LCYYF001), China, National Natural Science Foundation of China (NSFC 81271251). We thank Ruobing Zou for preparing blood samples from Canada. Statistical analysis was performed by Professor Yongjun Zhao, Department of Health Statistics, Binzhou Medical College of China. This study was supported by the research grants from National Natural Science Foundation of China (NSFC 81271251).
Author Contributions
Dr Fabin Han contributed to the research design, clinical diagnosis of PD patients, some experimental work and manuscript preparation; Dr Weidong Le contributed to the research design, clinical diagnosis of PD patients and manuscript corrections; Zhe Yu, Ting Wang, Dr Jun Xu, Wang Wang, Chao Chen, Lili Zheng, Li Pan, Fang Li, Lemuel Racacho contributed to the experimental work; Dr Bin Zhang, Dr Dianrong Gong, Dr Huaiqian Qu, Dr Guifang Wang, Dr Xueli Li and Dr Jun Xu contributed to clinical diagnosis of PD patients.
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Yu, Z., Wang, T., Xu, J. et al. Mutations in the glucocerebrosidase gene are responsible for Chinese patients with Parkinson’s disease. J Hum Genet 60, 85–90 (2015). https://doi.org/10.1038/jhg.2014.110
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DOI: https://doi.org/10.1038/jhg.2014.110
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