Abstract
In Lewy body disease, inflammation is discussed to be involved in the pathophysiological cascade. Osteopontin (OPN) is a multifunctional molecule, which is increased in inflammatory states. Here, we analyzed the allele frequency of two SNPs of the OPN gene, serum, and CSF OPN levels in Lewy body disease patients and controls. In accordance with our previous findings, we detected increased serum (P = 0.006) and CSF OPN levels (P = 0.0003) in the Lewy body disease cohort, compared to non-Lewy body disease subjects. The genotypic variation of SNP−66 was associated with the occurrence of Lewy body disease (odds ratio: 2.64, 95% CI 1.07–6.54, unadjusted P = 0.036). SNP+1239 was not related to Lewy body disease prevalence (odds ratio 1.61, 95% CI 0.66–3.91, P = 0.29). Genotype prevalence and OPN levels were not significantly related. These findings suggest that OPN is associated with the occurrence of Lewy body disease and SNP−66 may be a susceptibility factor.
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Benner EJ, Mosley RL, Destache CJ, Lewis TB, Jackson-Lewis V, Gorantla S et al (2004) Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 101:9435–9440
Brenner D, Labreuche J, Touboul PJ, Schmidt-Petersen K, Poirier O, Perret C et al (2006) Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients. Stroke 37:1691–1696
Burdo TH, Wood MR, Fox HS (2007) Osteopontin prevents monocyte recirculation and apoptosis. J Leukoc Biol 81:1504–1511
Chiocchetti A, Indelicato M, Bensi T, Mesturini R, Giordano M, Sametti S et al (2004) High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation. Blood 103:1376–1382
Chiocchetti A, Comi C, Indelicato M, Castelli L, Mesturini R, Bensi T et al (2005) Osteopontin gene haplotypes correlate with multiple sclerosis development and progression. J Neuroimmunol 163:172–178
Choi JS, Cha JH, Park HJ, Chung JW, Chun MH, Lee MY (2004) Transient expression of osteopontin mRNA and protein in amoeboid microglia in developing rat brain. Exp Brain Res 154:275–280
D’Alfonso S, Barizzone N, Giordano M, Chiocchetti A, Magnani C, Castelli L et al (2005) Two single-nucleotide polymorphisms in the 5′ and 3′ ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum 52:539–547
Forton AC, Petri MA, Goldman D, Sullivan KE (2002) An osteopontin (SPP1) polymorphism is associated with systemic lupus erythematosus. Hum Mutat 19:459
Giachelli CM, Steitz S (2000) Osteopontin: a versatile regulator of inflammation and biomineralization. Matrix Biol 19:615–622
Giachelli CM, Bae N, Almeida M, Denhardt DT, Alpers CE, Schwartz SM (1993) Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques. J Clin Invest 92:1686–1696
Guo H, Cai CQ, Schroeder RA, Kuo PC (2001) Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol 166:1079–1086
Han S, Guthridge JM, Harley IT, Sestak AL, Kim-Howard X, Kaufman KM et al (2008) Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. PLoS ONE 3:e0001757
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
Hummelshoj T, Ryder LP, Madsen HO, Odum N, Svejgaard A (2006) A functional polymorphism in the Eta-1 promoter is associated with allele specific binding to the transcription factor Sp1 and elevated gene expression. Mol Immunol 43:980–986
Hur EM, Youssef S, Haws ME, Zhang SY, Sobel RA, Steinman L (2007) Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat Immunol 8:74–83
Hwang SM, Lopez CA, Heck DE, Gardner CR, Laskin DL, Laskin JD et al (1994) Osteopontin inhibits induction of nitric oxide synthase gene expression by inflammatory mediators in mouse kidney epithelial cells. J Biol Chem 269:711–715
Iczkiewicz J, Rose S, Jenner P (2005) Increased osteopontin expression following intranigral lipopolysaccharide injection in the rat. Eur J Neurosci 21:1911–1920
Iczkiewicz J, Jackson MJ, Smith LA, Rose S, Jenner P (2006) Osteopontin expression in substantia nigra in MPTP-treated primates and in Parkinson’s disease. Brain Res 1118:239–250
Jellinger KA (1995) Neurodegenerative disorders with extrapyramidal features–a neuropathological overview. J Neural Transm Suppl 46:33–57
Kikuchi K, Tanaka A, Miyakawa H, Kawashima Y, Kawaguchi N, Matsushita M et al (2003) Eta-1/osteopontin genetic polymorphism and primary biliary cirrhosis. Hepatol Res 26:87–90
Lippa CF, Duda JE, Grossman M, Hurtig HI, Aarsland D, Boeve BF et al (2007) DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 68:812–819
Lopez CA, Hoyer JR, Wilson PD, Waterhouse P, Denhardt DT (1993) Heterogeneity of osteopontin expression among nephrons in mouse kidneys and enhanced expression in sclerotic glomeruli. Lab Invest 69:355–363
Maetzler W, Berg D, Schalamberidze N, Melms A, Schott K, Mueller JC et al (2007) Osteopontin is elevated in Parkinson’s disease and its absence leads to reduced neurodegeneration in the MPTP model. Neurobiol Dis 25:473–482
Marciano R, D’Annunzio G, Minuto N, Pasquali L, Santamaria A, Di Duca M et al (2009) Association of alleles at polymorphic sites in the osteopontin encoding gene in young type 1 diabetic patients. Clin Immunol. doi:10.1016/j.clim.2008.11.004 [Epub ahead of print]
McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872
Migliore L, Petrozzi L, Lucetti C, Gambaccini G, Bernardini S, Scarpato R et al (2002) Oxidative damage and cytogenetic analysis in leukocytes of Parkinson’s disease patients. Neurology 58:1809–1815
Niino M, Kikuchi S, Fukazawa T, Yabe I, Tashiro K (2003) Genetic polymorphisms of osteopontin in association with multiple sclerosis in Japanese patients. J Neuroimmunol 136:125–129
O’Regan A, Berman JS (2000) Osteopontin: a key cytokine in cell-mediated and granulomatous inflammation. Int J Exp Pathol 81:373–390
Reynolds AD, Banerjee R, Liu J, Gendelman HE, Mosley RL (2007) Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson’s disease. J Leukoc Biol 82:1083–1094
Rollo EE, Laskin DL, Denhardt DT (1996) Osteopontin inhibits nitric oxide production and cytotoxicity by activated RAW264.7 macrophages. J Leukoc Biol 60:397–404
Rosenkranz D, Weyer S, Tolosa E, Gaenslen A, Berg D, Leyhe T et al (2007) Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration. J Neuroimmunol 188:117–127
Scatena M, Liaw L, Giachelli CM (2007) Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol 27:2302–2309
Sodek J, Ganss B, McKee MD (2000) Osteopontin. Crit RevOral Biol Med 11:279–303
Tansey MG, Frank-Cannon TC, McCoy MK, Lee JK, Martinez TN, McAlpine FE et al (2008) Neuroinflammation in Parkinson’s disease: is there sufficient evidence for mechanism-based interventional therapy? Front Biosci 13:709–717
Wai PY, Kuo PC (2008) Osteopontin: regulation in tumor metastasis. Cancer Metastasis Rev 27:103–118
Wakabayashi K, Takahashi H, Takeda S, Ohama E, Ikuta F (1988) Parkinson’s disease: the presence of Lewy bodies in Auerbach’s and Meissner’s plexuses. Acta Neuropathol 76:217–221
Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML et al (2005) Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. Faseb J 19:533–542
Zohar R, Suzuki N, Suzuki K, Arora P, Glogauer M, McCulloch CA et al (2000) Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration. J Cell Physiol 184:118–130
Acknowledgments
We are grateful to Julia Hullmann and Heinrich Wiesinger for many helpful discussions. The authors wish to thank all patients, who took part in the study. The study was partly supported by the Robert Bosch Foundation (Number 32.5.1141.0019.0).
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Maetzler, W., Michelis, J., Tomiuk, J. et al. A single-nucleotide polymorphism of the osteopontin gene may contribute to a susceptibility to Lewy body disease. J Neural Transm 116, 599–605 (2009). https://doi.org/10.1007/s00702-009-0209-x
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DOI: https://doi.org/10.1007/s00702-009-0209-x