Association between alpha-synuclein (SNCA) rs11931074 variability and susceptibility to Parkinson’s disease: an updated meta-analysis of 41,811 patients
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.
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.
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.
SNCA rs11931074 polymorphism is found to be associated with PD risk and this risk appears to be influenced by genetic status and ethnicity.
KeywordsSNCA Polymorphism Parkinson’s disease Meta-analysis
This project was funded by the National Natural Science Foundation of China (grant number 81571299).
Compliance with ethical standards
This study was carried out in accordance with the recommendations of the Ethics Committee of Second Military Medical University.
Conflict of interest
The authors declare that they have no conflict of interest
- 9.Winkler S, Hagenah J, Lincoln S, Heckman M, Haugarvoll K, Lohmann HK, Kostic V, Farrer M, Klein C (2007) alpha-Synuclein and Parkinson disease susceptibility. Neurology 69:1745–1750. https://doi.org/10.1212/01.wnl.0000275524.15125.f4 CrossRefPubMedGoogle Scholar
- 12.Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, Kawaguchi T, Tsunoda T, Watanabe M, Takeda A, Tomiyama H, Nakashima K, Hasegawa K, Obata F, Yoshikawa T, Kawakami H, Sakoda S, Yamamoto M, Hattori N, Murata M, Nakamura Y, Toda T (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet 41:1303–1307. https://doi.org/10.1038/ng.485 CrossRefPubMedGoogle Scholar
- 13.Tan EK, Kwok HH, Tan LC, Zhao WT, Prakash KM, Au WL, Pavanni R, Ng YY, Satake W, Zhao Y, Toda T, Liu JJ (2010) Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus. Neurology 75:508–512. https://doi.org/10.1212/WNL.0b013e3181eccfcd CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Chen Y, Wei QQ, Ou R, Cao B, Chen X, Zhao B, Guo X, Yang Y, Chen K, Wu Y, Song W, Shang HF (2015) Genetic variants of SNCA are associated with susceptibility to Parkinson’s disease but not amyotrophic lateral sclerosis or multiple system atrophy in a Chinese population. PLoS One 10:e0133776. https://doi.org/10.1371/journal.pone.0133776 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Chung SJ, Jung Y, Hong M, Kim MJ, You S, Kim YJ, Kim J, Song K (2013) Alzheimer's disease and Parkinson’s disease genome-wide association study top hits and risk of Parkinson’s disease in Korean population. Neurobiol Aging 34:2695.e1–2695.e7. https://doi.org/10.1016/j.neurobiolaging.2013.05.022 CrossRefGoogle Scholar
- 18.Wu-Chou YH, Chen YT, Yeh TH, Chang HC, Weng YH, Lu CS (2013) Genetic variants of SNCA and LRRK2 genes are associated with sporadic PD susceptibility: a replication study in a Taiwanese cohort. Parkinsonism Relat Disord 19:251–255. https://doi.org/10.1016/j.parkreldis.2012.10.019 CrossRefPubMedGoogle Scholar
- 19.Ross OA, Gosal D, Stone JT, Lincoln SJ, Heckman MG, Irvine GB, Johnston JA, Gibson JM, Farrer MJ, Lynch T (2007) Familial genes in sporadic disease: Common variants of α-synuclein gene associate with Parkinson’s disease, Mech, Ageing. Dev. 128:378–382. https://doi.org/10.1016/j.mad.2007.04.002 CrossRefGoogle Scholar
- 20.Campelo CLC, Cagni FC, de Siqueira Figueredo D, Oliveira LG Jr, Silva-Neto AB, Macedo PT, Santos JR, Izidio GS, Ribeiro AM, de Andrade TG, de Oliveira Godeiro C Jr, Silva RH (2017) Variants in SNCA gene are associated with Parkinson’s disease risk and cog- nitive symptoms in a Brazilian sample. Front Aging Neurosci 9:198. https://doi.org/10.3389/fnagi.2017.00198 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Guo JF, Li K, Yu RL, Sun QY, Wang L, Yao LY, Jiang H, Yan XX, Pan Q, Xia K, Tang BS (2015) Polygenic determinants of Parkinson’s disease in a Chinese population. Neurobiol Aging 36:1765.e1761–1765.e1766. https://doi.org/10.1016/j.neurobiolaging.2014.12.030 CrossRefGoogle Scholar
- 24.Heckman MG, Elbaz A, Soto AI, Serie DJ, Aasly JO, Annesi G et al (2014) Protective effect of LRRK2 p.R1398H on risk of Parkinson’s disease is independent of MAPT and SNCA variants. Neurobiol Aging 35:266.e5–266.e14. https://doi.org/10.1016/j.neurobiolaging.2013.07.013 CrossRefGoogle Scholar