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Association between alpha-synuclein (SNCA) rs11931074 variability and susceptibility to Parkinson’s disease: an updated meta-analysis of 41,811 patients

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Abstract

Background and objectives

Parkinson’s disease (PD) is one of the most common forms of neurodegenerative disorders, and its etiology remains unclear. Single nucleotide polymorphisms (SNPs) of alpha-synuclein (SNCA) have been found to be significantly associated with PD risk. In particular, the variant rs11931074 was found in one meta-analysis to appear to play a role in the occurrence of PD. This finding has been questioned in subsequent studies, however. The aim of this study was to determine the relationship between PD risk and rs11931074 polymorphism.

Methods

We performed a systematic online search, including PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI (China National Knowledge Infrastructure), aiming to identify case–control studies looking at the role of rs11931074 in PD. We performed calculations of pooled odds ratio (OR) and 95% confidence interval (95% CI) to assess the associations, and subgroup meta-analyses to verify differences between various ethnicities of different study populations.

Results

A total of 13 studies involving 13,403 cases and 28,408 controls met the inclusion criteria after assessment by two reviewers. Overall, there exists significant associations between SNCA rs11931074 polymorphism and the risk of PD under five genetic models (allele contrast model: T vs. G, OR = 1.28, 95% CI = 1.12–1.45, P = 0.0001; homozygote model: TG vs. GG, OR = 1.55, 95% CI = 1.17–2.05, P = 0.002; heterozygote model (TT vs. GG, OR = 1.23, 95% CI = 1.05–1.42, P = 0.009; dominant model: TG+TT vs. GG: OR = 1.25, 95% CI = 1.05–1.50, P = 0.01 and recessive model: TT vs. TG+GG: OR = 1.40, 95% CI = 1.18–1.68, P = 0.0002). When ethnicities were stratified, significant associations were found in the allelic, homozygote, and recessive models for Asians, and in the allelic model for Caucasians.

Conclusion

SNCA rs11931074 polymorphism is found to be associated with PD risk and this risk appears to be influenced by genetic status and ethnicity.

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Funding

This project was funded by the National Natural Science Foundation of China (grant number 81571299).

Author information

Author notes

  1. Bingying Du, Qiang Xue, and Caiquan Liang equally contributed to this work

Authors and Affiliations

  1. Department of Neurology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China

    Bingying Du, Cunxiu Fan, Meng Liang & Xiaoying Bi

  2. Department of Neurology, General Hospital of Central Theater Command of Chinese People’s Liberation Army, Wuhan, China

    Bingying Du

  3. Department of Neurosurgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China

    Qiang Xue

  4. Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China

    Caiquan Liang

  5. Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada

    Yanbo Zhang

  6. Department of Neurosurgery, Shanghai Neurosurgical Institute, Changzheng Hospital, Second Military Medical University, Shanghai, China

    Lijun Hou

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  1. Bingying Du
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Correspondence to Xiaoying Bi or Lijun Hou.

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This study was carried out in accordance with the recommendations of the Ethics Committee of Second Military Medical University.

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Highlights

Association of SNCA gene polymorphisms (rs11931074) with PD susceptibility was examined.

SNCA rs11931074 polymorphism is found to increase risk in PD.

SNCA polymorphism SNP rs11931074 showed significant association in both Asian and Caucasian population.

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Du, B., Xue, Q., Liang, C. et al. Association between alpha-synuclein (SNCA) rs11931074 variability and susceptibility to Parkinson’s disease: an updated meta-analysis of 41,811 patients. Neurol Sci 41, 271–280 (2020). https://doi.org/10.1007/s10072-019-04107-8

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