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SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson’s disease in Chinese population

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Abstract

Background

Recently, rs2421947 in DNM3 (dynamin 3) was reported as a genetic modifier of age at onset (AAO) of LRRK2 G2019S-related Parkinson’s disease (PD) in a genome-wide association study in Arab-Berber population. Rs356219 in SNCA (α-synuclein) was also reported to regulate the AAO of LRRK2-related PD in European populations, and GAK (Cyclin G-associated kinase) rs1524282 was reported to be associated with an increased PD risk with an interaction with SNCA rs356219. G2019S variant is rare in Asian populations, whereas two other Asian-specific LRRK2 variants, G2385R and R1628P, are more frequent with a twofold increased risk of PD.

Methods

In this study, we investigated whether rs2421947, rs356219 and rs1524282 modified AAO in LRRK2-related PD patients in Han Chinese population. We screened LRRK2 G2385R and R1628P variants in 732 PD patients and 1992 healthy controls, and genotyped DNM3 rs2421947, SNCA rs356219 and GAK rs1524282 among the LRRK2 carriers.

Results

The SNCA rs356219-G allele was found to increase the risk of PD in LRRK2 carriers (OR 1.50, 95%CI 1.08–2.01, P = 0.016), and the AAO of AG + GG genotypes was 4 years earlier than AA genotype (P = 0.006). Nonetheless, no similar association was found in DNM3 rs2421947 and GAK rs1524282.

Conclusions

Our results show that SNCA but not DNM3 or GAK is associated with AAO of LRRK2-PD patients in Chinese population.

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Acknowledgements

We acknowledge all the participants including the PD patients and the healthy controls.

Funding

This work was supported by grants from the National Key R&D Program of China (Grant 2017YFA0105000), the National Natural Science Foundation of China to Dr. Chang-he Shi (Grant 81771290), and the National Natural Science Foundation of China to Dr. Yu-ming Xu (Grants 81530037 and 91849115).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she east road, Zhengzhou, 450000, Henan, China

    Zhi-hua Yang, Yu-sheng Li, Meng-meng Shi, Jing Yang, Yu-tao Liu, Cheng-yuan Mao, Yu Fan, Xin-chao Hu, Chang-he Shi & Yu-ming Xu

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  1. Zhi-hua Yang
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  2. Yu-sheng Li
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  3. Meng-meng Shi
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  4. Jing Yang
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  7. Yu Fan
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  9. Chang-he Shi
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Correspondence to Chang-he Shi or Yu-ming Xu.

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Yang, Zh., Li, Ys., Shi, Mm. et al. SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson’s disease in Chinese population. J Neurol 266, 1796–1800 (2019). https://doi.org/10.1007/s00415-019-09336-7

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  • DOI: https://doi.org/10.1007/s00415-019-09336-7

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