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Impact of infection on risk of Parkinson’s disease: a quantitative assessment of case-control and cohort studies

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Abstract

Identifying modifiable risk factors for Parkinson’s disease (PD) to help prevent this disease has attracted increasing interest in recent years for the limited effective drugs at present. Despite many studies indicated that infection acts as a risk factor for PD, there is no quantitative assessment of the impact of viral and bacterial infections on the risk of developing PD. The present study performed a meta-analysis on the basis of 38 datasets from 13 studies covering 287,773 PD cases and 7,102,901 controls to ascertain the association between PD and infection and the differences in the strength of the viral and bacterial infections. The overall meta-analytic results indicated that individuals with infection had a 20% increased risk of PD compared with controls (OR 1.20, 95%CI 1.07–1.32). The subgroup analysis according to the type of infection found that bacterial infection had a significant impact on increased risk of PD (OR 1.40, 95%CI 1.32–1.48). The present analysis indicated that infection could increase the risk of developing PD, and physician should be aware of the risk of developing PD in subjects with infection.

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References

  • Arai H, Furuya T, Mizuno Y, Mochizuki H (2006) Inflammation and infection in Parkinson’s disease. Histol Histopathol 21:673–678

    CAS  PubMed  Google Scholar 

  • Barcia C, Ros CM, Annese V, Gómez A, Ros-Bernal F, Aguado-Llera D, Martínez-Pagán ME, de Pablos V, Fernandez-Villalba E, Herrero MT (2012) IFN-gamma signaling, with the synergistic contribution of TNF-alpha, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s disease. Cell Death Dis 3:e379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214

    Article  CAS  PubMed  Google Scholar 

  • Bras JM, Singleton A (2009) Genetic susceptibility in Parkinson’s disease. Biochim Biophys Acta 1792:597–603

    Article  CAS  PubMed  Google Scholar 

  • Brown GC (2007) Mechanisms of inflammatory neurodegeneration: iNOS and NADPH oxidase. Biochem Soc Trans 35:1119–1121

    Article  CAS  PubMed  Google Scholar 

  • Bu XL, Wang X, Xiang Y, Shen LL, Wang QH, Liu YH, Jiao SS, Wang YR, Cao HY, Yi X, Liu CH, Deng B, Yao XQ, Xu ZQ, Zhou HD, Wang YJ (2015) The association between infectious burden and Parkinson’s disease: a case-control study. Parkinsonism Relat Disord 21:877–881

    Article  PubMed  Google Scholar 

  • Carvey PM, Chang QA, Ling Z (2004) Prenatal lipopolysaccharide (LPS) induces permanent reductions in dopamine neurons: effect of epigenetic alterations in CNS inflammatory homeostasis as an animal model for Parkinson's disease. Mov Disord 19:S151

    Article  Google Scholar 

  • Collier TJ, Kanaan NM, Kordower JH (2011) Ageing as a primary risk factor for Parkinson’s disease: evidence from studies of non-human primates. Nat Rev Neurosci 12:359–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Danzer M, Samberger C, Schicho R, Lippe IT, Holzer P (2004) Immunocytochemical characterization of rat brainstem neurons with vagal afferent input from the stomach challenged by acid or ammonia. Eur J Neurosci 19:85–92

    Article  PubMed  Google Scholar 

  • De Chiara G, Marcocci ME, Sgarbanti R, Civitelli L, Ripoli C, Piacentini R, Garaci E, Grassi C, Palamara AT (2012) Infectious agents and neurodegeneration. Mol Neurobiol 46:614–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang F, Wirdefeldt K, Jacks A, Kamel F, Ye W, Chen H (2012) CNS infections, sepsis and risk of Parkinson’s disease. Int J Epidemiol 41:1042–1049

    Article  PubMed  PubMed Central  Google Scholar 

  • Fletcher NF, Wilson GK, Murray J, Hu K, Lewis A, Reynolds GM, Stamataki Z, Meredith LW, Rowe IA, Luo G, Lopez-Ramirez MA, Baumert TF, Weksler B, Couraud PO, Kim KS, Romero IA, Jopling C, Morgello S, Balfe P, McKeating JA (2012) Hepatitis C virus infects the endothelial cells of the blood-brain barrier. Gastroenterology 142:634–643.e6

    Article  CAS  PubMed  Google Scholar 

  • Gao HM, Kotzbauer PT, Uryu K, Leight S, Trojanowski JQ, Lee VM (2008) Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci 28:7687–7698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D, Kay DM, Doheny KF, Paschall J, Pugh E, Kusel VI, Collura R, Roberts J, Griffith A, Samii A, Scott WK, Nutt J, Factor SA, Payami H (2010) Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet 42:781–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris MA, Tsui JK, Marion SA, Shen H, Teschke K (2012) Association of Parkinson’s disease with infections and occupational exposure to possible vectors. Mov Disord 27:1111–1117

    Article  PubMed  Google Scholar 

  • Huang HK, Wang JH, Lei WY, Chen CL, Chang CY, Liou LS (2018) Helicobacter pylori infection is associated with an increased risk of Parkinson’s disease: a population-based retrospective cohort study. Parkinsonism Relat Disord 47:26–31

    Article  CAS  PubMed  Google Scholar 

  • Jang H, Boltz DA, Webster RG, Smeyne RJ (2009) Viral Parkinsonism. Biochim Biophys Acta 1792:714–721

    Article  CAS  PubMed  Google Scholar 

  • Kim JM, Jang ES, Ok K, Oh ES, Kim KJ, Jeon B, Jo HJ, Ki M, Jeong SH (2016) Association between hepatitis C virus infection and Parkinson’s disease. Mov Disord 31:1584–1585

    Article  PubMed  Google Scholar 

  • Lai SW, Lin CH, Lin HF, Lin CL, Lin CC, Liao KF (2017) Herpes zoster correlates with increased risk of Parkinson’s disease in older people: a population-based cohort study in Taiwan. Medicine (Baltimore) 96:e6075

    Article  Google Scholar 

  • Lang AE, Lozan AM (1998) Parkinson’s disease. N Engl J Med 339:1044–1053

    Article  CAS  PubMed  Google Scholar 

  • Lees AJ, Hardy J, Revesz T (2009) Parkinson’s disease. Lancet 373:2055–2066

    Article  CAS  PubMed  Google Scholar 

  • Lema Tomé CM, Tyson T, Rey NL, Grathwohl S, Britschgi M, Brundin P (2013) Inflammation and α-synuclein’s prion-like behavior in Parkinson’s disease – is there a link? Mol Neurobiol 47:561–574

    Article  CAS  PubMed  Google Scholar 

  • Liu B, Gao HM, Hong JS (2003) Parkinson’s disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. Environ Health Perspect 111:1065–1073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martyn CN, Osmond C (1995) Parkinson’s disease and the environment in early life. J Neurol Sci 132(2):201–206

    Article  CAS  PubMed  Google Scholar 

  • Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269

    Article  PubMed  Google Scholar 

  • Nielsen HH, Qiu J, Friis S, Wermuth L, Ritz B (2012) Treatment for Helicobacter pylori infection and risk of Parkinson’s disease in Denmark. Eur J Neurol 19:864–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pakpoor J, Noyce A, Goldacre R, Selkihova M, Mullin S, Schrag A, Lees A, Goldacre M (2017) Viral hepatitis and Parkinson disease: a national record-linkage study. Neurology 88:1630–1633

    Article  PubMed  Google Scholar 

  • Parkinson J (2002) An essay on the shaking palsy. 1817. J Neuropsychiatr Clin Neurosci 14:223–236

    Article  Google Scholar 

  • Pringsheim T, Jette N, Frolkis A, Steeves TD (2014) The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 29:1583–1590

    Article  PubMed  Google Scholar 

  • Ritz B, Ascherio A, Checkoway H, Marder KS, Nelson LM, Rocca WA, Ross GW, Strickland D, Van Den Eeden SK, Gorell J (2007) Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol 64:990–997

    Article  PubMed  Google Scholar 

  • Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283:2674–2679

    Article  CAS  PubMed  Google Scholar 

  • Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137:47–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schapira AH (2006) Etiology of Parkinson’s disease. Neurology 66:S10–S23

    Article  PubMed  Google Scholar 

  • Shen CH, Chou CH, Liu FC, Lin TY, Huang WY, Wang YC, Kao CH (2016) Association between tuberculosis and Parkinson disease: a nationwide, population-based cohort study. Medicine (Baltimore) 95:e2883

    Article  Google Scholar 

  • Takahashi M, Yamada T, Nakajima S, Nakajima K, Yamamoto T, Okada H (1995) The substantia nigra is a major target for neurovirulent influenza a virus. J Exp Med 181:2161–2169

    Article  CAS  PubMed  Google Scholar 

  • Tsai HH, Liou HH, Muo CH, Lee CZ, Yen RF, Kao CH (2016) Hepatitis C virus infection as a risk factor for Parkinson disease: a nationwide cohort study. Neurology 86:840–846

    Article  PubMed  Google Scholar 

  • Vila M, Przedborski S (2004) Genetic clues to the pathogenesis of Parkinson’s disease. Nat Med 10(suppl):S58–S62

    Article  CAS  PubMed  Google Scholar 

  • Vlajinac H, Dzoljic E, Maksimovic J, Marinkovic J, Sipetic S, Kostic V (2013) Infections as a risk factor for Parkinson’s disease: a case-control study. Int J Neurosci 123:329–332

    Article  PubMed  Google Scholar 

  • Weissenborn K, Ennen JC, Bokemeyer M, Ahl B, Wurster U, Tillmann H, Trebst C, Hecker H, Berding G (2006) Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment. Gut 55:1624–1630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitton PS (2007) Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol 150:963–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu WY, Kang KH, Chen SL, Chiu SY, Yen AM, Fann JC, Su CW, Liu HC, Lee CZ, Fu WM, Chen HH, Liou HH (2015) Hepatitis C virus infection: a risk factor for Parkinson’s disease. J Viral Hepat 22:784–791

    Article  CAS  PubMed  Google Scholar 

  • Zhou L, Miranda-Saksena M, Saksena NK (2013) Viruses and neurodegeneration. Virol J 10:172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Shandong Provincial Natural Science Foundation (Grant Nos. JQ201508 and ZR2018MH010), Shandong Provincial Key Research and Development Program (Grant No. 2018GSF121001), and Talent program of Zibo.

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Authors and Affiliations

  1. Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People’s Republic of China

    Lei Meng, Liang Shen & Hong-Fang Ji

  2. Zibo Key Laboratory for Neurodegenerative Diseases Drug Development, Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, People’s Republic of China

    Lei Meng, Liang Shen & Hong-Fang Ji

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  1. Lei Meng
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  2. Liang Shen
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  3. Hong-Fang Ji
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Contributions

L.S. and H.F.J. conceived and designed the study, L.M. and L.S.collected data and performed analysis, L.M., L.S., and H.F.J. analyzed the data and wrote the main manuscript text. All authors read and approved the final manuscript.

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Correspondence to Liang Shen or Hong-Fang Ji.

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Meng, L., Shen, L. & Ji, HF. Impact of infection on risk of Parkinson’s disease: a quantitative assessment of case-control and cohort studies. J. Neurovirol. 25, 221–228 (2019). https://doi.org/10.1007/s13365-018-0707-4

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