It is increasingly recognized that genetic variants play a significant role in the development of a range of common diseases as well as in the individual response to medications. Identifying genetic risk factors for the development of epilepsy and response to antiepileptic drug therapy can lead to major advances in our understanding of the pathogenesis of epilepsy and of drug resistance, leading to new treatment targets and strategies. However, progress in the research as well as application of findings in epilepsy genetics in developing countries, such as rural China, is hampered by deficiency in accurate diagnosis and phenotyping because of lack of specialist expertise and sophisticated investigation techologies. To overcome this critical research and clinical barrier, this research aims to develop the necessary infrastructure through the development and validation of clinical assessment tools for accurate phenotyping and building genetics research capacity, including research logistics, network and personnel training. The research model developed has the potential to be applied in other low- and middle-income countries, where 80% of the world's 50 million epilepsy patients live. Clinical assessment tools (questionnaires) will be developed for phenotyping of epilepsy, focusing on the classification of various seizure types and epilepsy syndromes which have implications for drug choice and prognosis. To validate the assessment tools, they will be applied by village doctors after training to 600 patients selected from the Chinese government's national epilepsy treatment programs. The validity of the clinical assessment tools in phenotyping will be determined by comparing with the gold standard, comprising of specialist evaluation, electroencephalography recording and magnetic resonance imaging of the brain. To obtain preliminary data in identifying genetic marker loci predictive of increased susceptibility to epilepsy, a buccal smear/saliva sample will be obtained from each patient for DNA extraction and subsequent genotyping. Frequencies of the polymorphisms will be compared between patients and controls. Candidate polymorphisms will be selected from significant variants identified in a genome wide association study being carried out in an independent cohort of Chinese epilepsy patients.
Affecting 50 million people worldwide with 80% living in resource poor countries, epilepsy is the most common neurological disorder and a major global public health issue. Understanding the genetic risk factors predisposing to epilepsy and drug resistance can help doctors find better treatment and potentially preventive therapy, but patients in developing countries are often excluded from such research because of lack of expertise and sophisticated investigation technologies to classify the different types of epilepsy.
This research aims to develop the necessary infrastructure for conducting large scale genetics research in rural China through the development and validation of clinical assessment tools for accurate phenotyping and building genetics research capacity, including research logistics, network and personnel training.