Mitochondrial DNA Mutation in Thyroid Disease

• Main Authors: Hung-Cheng Chou, 周鴻誠
• Other Authors: Shu-Huei Kao
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/88457057467386555415

碩士 === 臺北醫學大學 === 醫學技術學系 === 93 === Abstract Goiter and benign thyroid disease are a common problem with prevalence about 4％ in the general population. The pathogenesis of goiter and gland hyperplasia is still unclear. Human mtDNA is recognized to evolve 10–100 times faster than nuclear DNA with a number of reasons. Those most often reported are the aggressive environment rich in ROS to mitochondrlia and caused oxidative damage of Mitochondrial DNA . Accumlation of human mtDNA mutations has been demonstrated to be an important factor of human aging and degenerative disease. Thyroid hormone exert profound effects on the energy metabolis- m thus extremely vulnerable to oxidative damage by ROS and other free radicals generated as by products in the electron transport chain. It is well defined that thyroid hormone could contribute in the regulation of the expression of mtDNA replication and nucleus encoded mitochondrial protein. Forty patients with thyroid hyperplasia patient from Shin-Chu Hospital were enrolled in this study. We also collected the clinical data of TSH、T3 and free T4. The large-scale mtDNA deletion were identified by long-rang PCR, primer -shift PCR and semi-quantitative PCR. Thyroid tissue and blood samples were collected and applied to the analysis of mtDNA mutation .There were three types of mtDNA deletion identified in this study including 4977bp, 7599bp and 5335 bp deletions. The highest frequencies of occurrence in mtDNA deletion were found in the papillary carcinoma is (67.3%). The occurrence of mtDNA deletion was 67.3%, 37.5% and 20.0% in papillary carcinoma, Nodular hyperplasia, and diffuse hyperplasia, respectively. Abnormal hormone level were correlated with the occurrence of mtDNA deletion. TSH level abnormal bearing with 7599bp deletion was about 62.5%, with 5335bp deletion was about 37.5%, with 4977bp deletion was about 25.0%. T4 level abnormal bearing with 7599bp deletion was about 80.0%, with 5335bp deletion was about80.0%, with 4977bp deletion was about 60.0%. The mtDNA copy-number were detected by real-time PCR and we finned that mtDNA copy-number were decreased in tissue sample of patient (52%). The mtDNA copy-number in the blood sample of patient after operation was increase about 10％ than patient before operation. It reveals that patient after operation treatment may increase there mtDNA copy-number. We suggest that mutations and/or depletion of mtDNA might play some important role in the progression and pathogenesis of thyroid hyperplasia.