Apolipoprotein E Polymorphisms and Parkinson Disease With or Without Dementia: A Meta-Analysis Including 6453 Participants

Abstract

A large number of case–control studies have investigated the association of apolipoprotein E (APOE) polymorphisms with Parkinson disease (PD) and Parkinson disease dementia (PDD), with inconsistent results. This meta-analysis aimed to evaluate the relationship between APOE polymorphisms and PD/PDD risk. We searched for published studies in PubMed, Web of Science, WanFang Data (in Chinese), and CNKI (in Chinese) from inception to June 2017. Case–control studies reporting part or complete APOE genotype and allele frequency data were included. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using RevMan 5.3 software. A total of 39 studies involving 6453 cases with PD, with 461 cases with PDD, and 6855 controls were included in this meta-analysis. The results showed that the APOE ε3 allele was a protective factor for PD (OR = 0.90, 95% CI: 0.81-0.99; P = .04), whereas no significant differences in PD risk among all cases compared to controls were found for APOE ε2 and ε4. In Asian subgroups, the APOE ε4 allele was shown to be a risk factor for PD (OR = 1.22, 95% CI: 1.01-1.46; P = .04). Additionally, APOE polymorphisms were significantly associated with PDD risk in the entire case group (ε3: OR = 0.72, 95% CI: 0.58-0.89, P = .003; ε4: OR = 1.46, 95% CI: 1.12-1.88, P = .004) and in Asian subgroups.

Keywords

apolipoprotein E polymorphisms Parkinson disease Parkinson disease dementia meta-analysis

Get full access to this article

View all access options for this article.

References

de Lau

Breteler

. Epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5(6):525–535.

Berlyand

Weintraub

Xie

. An Alzheimer’s disease-derived biomarker signature identifies Parkinson’s disease patients with dementia. PLoS One. 2016;11(1):e0147319.

Xing

Tang

Zhao

. Associations between plasma ceramides and cognitive and neuropsychiatric manifestations in Parkinson’s disease dementia. J Neurol Sci. 2016;370:82–87.

Federoff

Jimenez-Rolando

Nalls

. A large study reveals no association between APOE and Parkinson’s disease. Neurobiol Dis. 2012;46(2):389–392.

Gregorio

Pinhel

Sado

. Impact of genetic variants of apolipoprotein E on lipid profile in patients with Parkinson’s disease. Biomed Res Int. 2013;2013:641515.

Strittmatter

Roses

. Apolipoprotein E and Alzheimer’s disease. Annu Rev Neurosci. 1996;19:53–77.

Lopez

Guerrero

Yescas

. Apolipoprotein E epsilon4 allele is associated with Parkinson disease risk in a Mexican Mestizo population. Mov Disord. 2007;22(3):417–420.

Papapetropoulos

Farrer

Stone

. Phenotypic associations of tau and ApoE in Parkinson’s disease. Neurosci Lett. 2007;414(2):141–144.

Gallegos-Arreola

Figuera

Ortiz

. Apolipoprotein E genotypes in Mexican patients with Parkinson’s disease. Dis Markers. 2009;27(5):225–230.

10.

Singh

Banerjee

Bala

. APOE and LRPAP1 gene polymorphism and risk of Parkinson’s disease. Neurol Sci. 2014;35(7):1075–1081.

11.

Pulkes

Papsing

Mahasirimongkol

. Association between apolipoprotein E genotypes and Parkinson’s disease. J Clin Neurosci. 2011;18(10):1333–1335.

12.

Eerola

Launes

Hellstrom

. Apolipoprotein E (APOE), PARKIN and catechol-O-methyltransferase (COMT) genes and susceptibility to sporadic Parkinson’s disease in Finland. Neurosci Lett. 2002;330(3):296–298.

13.

Williams-Gray

Goris

Saiki

. Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s disease. J Neurol. 2009;256(3):493–498.

14.

Vefring

Haugarvoll

Tysnes

. The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study. Acta Neurol Scand. 2010;122(6):438–441.

15.

Mata

Leverenz

Weintraub

. APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA Neurol. 2014;71(11):1405–1412.

16.

Pavlova

Mehrabian

Petrova

. Cognitive, neuropsychiatric, and motor features associated with apolipoprotein E epsilon4 allele in a sample of Bulgarian patients with late-onset Parkinson’s disease. Am J Alzheimers Dis Other Demen. 2014;29(7):614–619.

17.

Zintzaras

Ioannidis

. Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol. 2005;28(2):123–137.

18.

Higgins

Thompson

Deeks

. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–560.

19.

Higgins

Thompson

. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–1558.

20.

Mantel

Haenszel

. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–748.

21.

Chao

Wong

Tan

. Evidence of inflammatory system involvement in Parkinson’s disease. Biomed Res Int. 2014;2014:308654.

22.

Lill

. Genetics of Parkinson’s disease. Mol Cell Probes. 2016;30(6):386–396.

23.

Troster

Fields

Paolo

. Absence of the apolipoprotein E epsilon4 allele is associated with working memory impairment in Parkinson’s disease. J Neurol Sci. 2006;248(1-2):62–67.

24.

Tsuang

Leverenz

Lopez

. APOE epsilon4 increases risk for dementia in pure synucleinopathies. JAMA Neurol. 2013;70(2):223–228.

25.

Apolipoprotein E genotype in familial Parkinson’s disease. The French Parkinson’s disease genetics study group. J Neurol Neurosurg Psychiatry. 1997;63(3):394–395.

26.

Camicioli

Rajput

. Apolipoprotein E epsilon4 and catechol-O-methyltransferase alleles in autopsy-proven Parkinson’s disease: relationship to dementia and hallucinations. Mov Dis. 2005;20(8):989–994.

27.

Kiyohara

Miyake

Koyanagi

. APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson’s disease in a Japanese population. J Neural Trans. 2011;118(9):1335–1344.

28.

Huang

Chen

Kaufer

. Apolipoprotein E and dementia in Parkinson disease: a meta-analysis. Arch Neurol. 2006;63(2):189–193.

29.

Bon

Jansen Steur

de Vos

. Neurogenetic correlates of Parkinson’s disease: apolipoprotein-E and cytochrome P450 2D6 genetic polymorphism. Neurosci Lett. 1999;266(2):149–151.

30.

Hao

Xie

. Association between polymorphism of alpha 1-antichymotrypsin and apolipoprotein E gene and Parkinson’s disease in Shanghai Hans [in Chinese]. Zhonghua Yi Xue Za Zhi. 2001;81(19):1172–1175.

31.

Ezquerra

Campdelacreu

Gaig

. Lack of association of APOE and tau polymorphisms with dementia in Parkinson’s disease. Neurosci Lett. 2008;448(1):20–23.

32.

Mengel

Dams

Ziemek

. Apolipoprotein E epsilon4 does not affect cognitive performance in patients with Parkinson’s disease. Parkinsonism Relat Disord. 2016;29:112–116.

33.

Harhangi

de Rijk

van Duijn

. APOE and the risk of PD with or without dementia in a population-based study. Neurology. 2000;54(6):1272–1276.

34.

Ghebremedhin

Del Tredici

Vuksic

. Relationship of apolipoprotein E and age at onset to Parkinson disease neuropathology. J Neuropathol Exp Neurol. 2006;65(2):116–123.

35.

Jasinska-Myga

Opala

Goetz

. Apolipoprotein E gene polymorphism, total plasma cholesterol level, and Parkinson disease dementia. Arch Neurol. 2007;64(2):261–265.

36.

Gao

Huang

Park

. Apolipoprotein E genotypes and the risk of Parkinson disease. Neurobiol Aging. 2011;32(11):2106.e1–6.

37.

Riedel

Thompson

Brinton

. Age, APOE and sex: triad of risk of Alzheimer’s disease. J Steroid Biochem Mol Biol. 2016;160:134–147.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.18 MB

0.07 MB