Variation and Regulation of Parkinson's Disease Associated Gene, TH and COMT

• Main Author: 鄭光琪
• Other Authors: 徐雲鵬
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/78401431755862427384

碩士 === 國立清華大學 === 生命科學系 === 87 === Parkinson's disease (PD) is a neurodegenerative disease characterized primarily by loss of nigrostriatal dopaminergic neurons and consequent depletion of dopamine. To date the underlying cause of PD is still unknown. It is suggested that interplay between environmental factors and genes may be involved in the pathogenesis of PD. Genetic variations in enzymes which act on biosynthesis or degradation of dopamine and its metabolites may also influence susceptibility to PD. Tyrosine hydroxylase (TH) catalyzes L-tyrosine to 3,4-dihydroxyphenylalanine (L-dopa). In dopamine biosynthesis pathway, TH is involved in the rate-limiting step. Catechol O-methyltransferase (COMT) plays an important role in the degradation pathway of dopamine. In this study, we investigated the association between COMT and TH gene variations and PD. By PCR and RFLP, we found that COMT and TH gene variations are associated with PD. The 5' noncoding regions of TH and COMT were then scanned for variations. New variations in 5' noncoding regions of TH and COMT genes were identified, including a BsmAI RFLP. However, the BsmAI polymorphism in TH 5' noncoding region is not associated with PD. Cell culture systems were set up to study the effect of growth factors on the expression of COMT and TH at transcriptional level. Our preliminary result may indicate tissue specificity and variations in gene expression.