An Association Study of Mitochondrial Function Related Genes and Ischemic Stroke

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Stroke is the third leading cause of death and an important source of disability in Taiwan. The majority of stroke is ischemic stroke. Oxidative stress, such as reactive oxygen species (ROS), has been reported to play a key role on the development of ischemic stroke. Mitochondria are the major cellular source of ROS. Mitochondrial dysfunction would increase ROS resulting in impaired aerobic capacity, endothelial dysfunction, vascular smooth muscle cell proliferation or apoptosis, and ultimately, the development of atherosclerosis and atherosclerotic plaque, which are the important causes of ischemic stroke. However, research data on the joint effect between mitochondrial function related genes and cardiovascular disease risk factors on the risk and severity of ischemic stroke are scarce. In this project, a total of 1000 ischemic stroke cases confirmed with computerized tomographic scan and/or magnetic resonance imaging will be recruited from seven participating hospitals in Formosa Stroke Genetic Consortium (FSGC). A total of 1000 healthy controls will be frequency-matched by age and sex with cases and recruited from the health examinations from SKH, TMUH, SHH and WFH. A structured questionnaire will be used to collect the information of life style and biological risk factors from all study subjects. Stroke severity will be determined by the scores of NIH Stroke Scale at admission. Genotyping of mitochondrial DNA (MT-ND, MT-CO, and MT-ATP), mitochondrial dynamics related genes (MFN1, MFN2, OPA1, DRP1, and FIS1), and mitochondrial biogenesis related genes (PPARGC1A, NRF-1, NRF-2, and TFAM) will be determined by the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time polymerase chain reaction (RT-PCR). This three-year project aims to 1) evaluate the association between mitochondrial function related genes (mitochondrial DNA : MT-ND, MT-CO, and MT-ATP; mitochondrial dynamics: MFN1, MFN2, OPA1, DRP1, and FIS1; mitochondrial biogenesis: PPARGC1A, NRF-1, NRF-2, and TFAM) and the risk of ischemic stroke; 2) to investigate the correlation between the mitochondrial function related genes and severity of ischemic stroke; 3) to explore the joint effect of gene-gene and gene-environment on the risk and severity of ischemic stroke; 4) to investigate the modify effect of mitochondrial function related genes on the traditional cardiovascular risk factor for the risk and severity of ischemic stroke
StatusFinished
Effective start/end date8/1/147/31/15

Keywords

  • ischemic stroke
  • mitochondrial DNA
  • mitochondrial dynamics
  • mitochondrial biogenesis