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Genetic analysis of heme oxygenase-1 (HO-1) in German Parkinson’s disease patients

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons and the presence of intracytoplasmic inclusions (Lewy bodies). Iron, which is elevated in the substantia nigra (SN) of PD patients, seems to be of pivotal importance, because of its capacity to enhance the amplification of reactive-oxygen species. Therefore, it is tempting that the iron-releasing key enzyme in heme catabolism, heme oxygenase-1 (HO-1), may represent a candidate for a genetic susceptibility to PD. In the current study, we examined a (GT)n fragment length polymorphism in the promoter region, as well as three coding SNPs in the HO-1 gene in order to assess if certain genotypes are associated with PD. Furthermore, peripheral blood expression levels of HO-1 in PD patients and healthy probands were compared. However, our analyses did not reveal a significant association of these genetic markers in the HO-1 gene with an increased susceptibility to PD.

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Abbreviations

AD:

Alzheimer’s disease

HO-1 :

Heme oxygenase-1

PD:

Parkinson’s disease

qRT-PCR:

Quantitative real-time PCR

ROS:

Reactive-oxygen species

SN:

Substantia nigra

SNP:

Single-nucleotide polymorphism

TCS:

Transcranial sonography

References

  • Baranano DE, Snyder SH (2001) Neural roles for heme oxygenase: contrasts to nitric oxide synthase. Proc Natl Acad Sci USA 98:10996–11002

    Article  PubMed  CAS  Google Scholar 

  • Berg D (2006) Transcranial sonography in the early and differential diagnosis of Parkinson’s disease. J Neural Transm Suppl 24:9–254

    Google Scholar 

  • Berg D, Becker G, Zeiler B et al (1999) Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 53:1026–1031

    PubMed  CAS  Google Scholar 

  • Berg D, Gerlach M, Youdim MB et al (2001a) Brain iron pathways and their relevance to Parkinson’s disease. J Neurochem 79:225–236

    Article  PubMed  CAS  Google Scholar 

  • Berg D, Jabs B, Merschdorf U et al (2001b) Echogenicity of substantia nigra determined by transcranial ultrasound correlates with severity of parkinsonian symptoms induced by neuroleptic therapy. Biol Psychiatry 50:463–467

    Article  PubMed  CAS  Google Scholar 

  • Berg D, Roggendorf W, Schroder U et al (2002) Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 59:999–1005

    Article  PubMed  Google Scholar 

  • Berg D, Hochstrasser H, Schweitzer KJ et al (2006) Disturbance of iron metabolism in Parkinson’s disease—ultrasonography as a biomarker. Neurotox Res 9:1–13

    Article  PubMed  CAS  Google Scholar 

  • Cary NC (ed) (2003) SAS User’s Guide: Statistics. SAS Institute Inc

  • Chen YH, Lin SJ, Lin MW et al (2002) Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients. Hum Genet 111:1–8

    Article  PubMed  CAS  Google Scholar 

  • Dennery PA (2000) Regulation and role of heme oxygenase in oxidative injury. Curr Top Cell Regul 36:181–199

    Article  PubMed  CAS  Google Scholar 

  • Dore S, Takahashi M, Ferris CD et al (1999) Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Proc Natl Acad Sci USA 96:2445–2450

    Article  PubMed  CAS  Google Scholar 

  • Frankel D, Mehindate K, Schipper HM (2000) Role of heme oxygenase-1 in the regulation of manganese superoxide dismutase gene expression in oxidatively-challenged astroglia. J Cell Physiol 185:80–86

    Article  PubMed  CAS  Google Scholar 

  • Fung HC, Scholz S et al (2006) Genome-wide genotyping in Parkinson`s disease and neurologically normal controls: first stage analysis and public release of data. Lancet Neurol 5:911–916

    Article  PubMed  CAS  Google Scholar 

  • Hellemans J, Mortier G, De Paepe A et al (2007) qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol 8:R19

    Article  PubMed  CAS  Google Scholar 

  • Kikuchi A, Yamaya M, Suzuki S et al (2005) Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism. Hum Genet 116:354–360

    Article  PubMed  CAS  Google Scholar 

  • Kimpara T, Takeda A, Watanabe K et al (1997) Microsatellite polymorphism in the human heme oxygenase-1 gene promoter and its application in association studies with Alzheimer and Parkinson disease. Hum Genet 100:145–147

    Article  PubMed  CAS  Google Scholar 

  • Kutty RK, Kutty G, Rodriguez IR et al (1994) Chromosomal localization of the human heme oxygenase genes: heme oxygenase-1 (HMOX1) maps to chromosome 22q12 and heme oxygenase-2 (HMOX2) maps to chromosome 16p13.3. Genomics 20:513–516

    Article  PubMed  CAS  Google Scholar 

  • Lee DW, Andersen JK, Kaur D (2006) Iron dysregulation and neurodegeneration: the molecular connection. Mol Interv 6:89–97

    Article  PubMed  CAS  Google Scholar 

  • Llesuy SF, Tomaro ML (1994) Heme oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage. Biochim Biophys Acta 1223:9–14

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka Y, Kitamura Y, Okazaki M et al (1998) Kainic acid induction of heme oxygenase in vivo and in vitro. Neuroscience 85:1223–1233

    Article  PubMed  CAS  Google Scholar 

  • Mizuta I, Satake W et al (2006) Multiple candidate gene analysis identifies alpha-synuclein as a susceptibility gene for sporadic Parkinson`s disease. Hum Mol Genet 15:1151–1158

    Article  PubMed  CAS  Google Scholar 

  • Nakagami T, Toyomura K, Kinoshita T et al (1993) A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin. Biochim Biophys Acta 1158:189–193

    PubMed  CAS  Google Scholar 

  • Raymond M, Rousset F (1995) GENEPOP (Version 1.2): Population Genetics Software for Exact Tests and Ecumenicism 86:248–249

  • Rouault TA (2001) Systemic iron metabolism: a review and implications for brain iron metabolism. Pediatr Neurol 25:130–137

    Article  PubMed  CAS  Google Scholar 

  • Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S (eds) Bioinformatics methods and protocols: methods in molecular biology. Humana Press, Totowa

    Google Scholar 

  • Schipper HM (2000) Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol 35:821–830

    Article  PubMed  CAS  Google Scholar 

  • Schipper HM (2004a) Brain iron deposition and the free radical-mitochondrial theory of ageing. Ageing Res Rev 3:265–301

    Article  PubMed  CAS  Google Scholar 

  • Schipper HM (2004b) Heme oxygenase-1: transducer of pathological brain iron sequestration under oxidative stress. Ann N Y Acad Sci 1012:84–93

    Article  PubMed  CAS  Google Scholar 

  • Schipper HM, Liberman A, Stopa EG (1998) Neural heme oxygenase-1 expression in idiopathic Parkinson’s disease. Exp Neurol 150:60–68

    Article  PubMed  CAS  Google Scholar 

  • Shibahara S (1994) Heme oxygenase–regulation of and physiological implication in heme catabolism. In: Fujita H (ed) Regulation of heme protein synthesis. AlphaMed Press, Dayton

    Google Scholar 

  • Stocker R, Yamamoto Y, McDonagh AF et al (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046

    Article  PubMed  CAS  Google Scholar 

  • Yamada N, Yamaya M, Okinaga S et al (2000) Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet 66:187–195

    Article  PubMed  CAS  Google Scholar 

  • Yasuda H, Okinaga S, Yamaya M et al (2006) Association of susceptibility to the development of pneumonia in the older Japanese population with heme oxygenase-1 gene promoter polymorphism. J Med Genet 43:e17

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Piantadosi CA (1992) Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J Clin Invest 90:1193–1199

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Claudia Schulte (Hertie Institute of Clinical Brain Research, University of Tuebingen) for technical assistance and for helpful discussions. This work was supported by the National Genome Research Network (NGFNplus).

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Correspondence to Anne S. Soehn.

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Funke, C., Tomiuk, J., Riess, O. et al. Genetic analysis of heme oxygenase-1 (HO-1) in German Parkinson’s disease patients. J Neural Transm 116, 853–859 (2009). https://doi.org/10.1007/s00702-009-0237-6

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  • DOI: https://doi.org/10.1007/s00702-009-0237-6

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