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Sökning: WFRF:(Zettergren Anna 1978) > Doktorsavhandling > Genetics of Parkins...

Genetics of Parkinson's disease - with focus on genes of relevance for inflammation and dopamine neruon development

Zettergren, Anna, 1978 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
 (creator_code:org_t)
ISBN 9789162880224
2010
Engelska.
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Abstract GENETICS OF PARKINSON’S DISEASE - WITH FOCUS ON GENES OF RELEVANCE FOR INFLAMMATION AND DOPAMINE NEURON DEVELOPMENT Introduction: The risk to be affected by Parkinson’s disease (PD) is considered to be influenced by genetic factors. In some rare cases of familial PD, mutations in some specific genes are known to cause the disease, but in the more common sporadic form of PD the causes are probably environmental factors interacting with genetic vulnerability. The main objective of this thesis was to identify genes of importance for this genetic vulnerability in sporadic PD, by analysing the frequency of polymorphisms in PD patients and control subjects. The investigated genes encode proteins involved in one, or both, of two processes suggested to be of importance for the pathophysiology of PD; inflammation and development of dopaminergic neurons. Main observations: A single nucleotide polymorphism (SNP) in the gene encoding estrogen receptor beta was found to be associated with PD with an early age of onset. Furthermore, this SNP seems to interact with a SNP in the gene for the pro-inflammatory cytokine interleukin 6, potentiating the susceptibility to PD, especially among early age of onset patients. In the genes encoding the anti-inflammatory cytokine interleukin 10 and the dopaminergic transcription factor Pitx3, polymorphisms associated with age of onset were identified. Conclusions: The results indicate that several of the investigated genes might be of importance for the pathophysiology of sporadic PD. Often the polymorphisms were associated only with PD with an early age of onset, possibly explained by a more important role of genetic factors among patients with an early onset. An alternative explanation is that some of the polymorphisms affect the age of onset of PD, for example by modulating the vulnerability to disease-causing environmental factors. The relevance of the present results can only be confirmed by additional studies in other PD populations. For some of the genes the results of the present thesis have been replicated, while for others no additional studies have been published or the findings have not been confirmed.

Nyckelord

Parkinson's disease
genetics
inflammation
single nucleotide polymorphism
dopamine neuron development
estrogen
gene
age of onset
Pitx3
estrogen receptor beta
interleukin 6

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dok (ämneskategori)

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Göteborgs universitet

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