Study On Risk Factors For Epileptic Attack And Genetic Epidemiology Of Idiopathic Epilepsy

Epilepsy is a chronic brain disease with complex etiology. Now there have been many theories (cell theory, neurotransmitters, ion channels and immunization theory, etc.) for the cause and pathogenesis of epilepsy. The main risk factors of epilepsy are family history, congenital and perinatal abnormalities, head injury, central nervous system infection, cerebrovascular disease. In recent years, numerous studies at home and abroad showed that genetic factors were important risk factors of epilepsy while other various theories based on genetics. Epilepsy is the result of interaction of genetic factors and External factors which lead to brain damage.The aims of present study are to explore the risk factors of epilepsy and probe the genetic model of the idiopathic epilepsy based on case-control study of clinical examination, furthermore the effect to it. We have collected eligible data of the epileptic patients, the control ones and their pedigrees by uniform questionnaire then set up the epidemiologic database of epilepsy in Acess2007. After proper transformation the data were statistically analyzed by statistics analysis system (SAS9.2), statistic snalysis of genetic epidemiology (S.A.GE.6.0.1) and methods of Falconer's and Li-Mantel-Gart in order to conduct case-control study of risk factors, complex segregation analysis, calculation of heritability and separation ratio.Major study results:(1) Finally, there are 600 cases of epilepsy,361 cases of control to meet the inclusion and exclusion criteria. We have established a collecting system for 600 epileptic probands'pedigrees and 361 control'pedigrees correspondingly, while there are 515 idiopathic epileptic pedigrees.(2) Case-control study on risk factors of epilepsy:①Risk factors influencing epilepsy include family history of epilepsy (OR=10.201), history of febrile convulsion (OR=5.110), frequent exercise (OR=4.953), poorer psychology (OR=5.430), and history of craniocerebral injury (OR=2.242).②The risk factors of idiopathic epilepsy are family history of epilepsy (OR=14.080), history of febrile convulsion(OR=4.421) and poorer psychology (OR=4.371); the risk factors of secondary epilepsy include history of craniocerebral injury(OR=4.713), history of febrile convulsion(OR=10.840), and birth trauma (OR=4.261).③Risk factors of generalized seizure are family history of epilepsy (OR=8.365), history of febrile convulsion(OR=4.920) and poorer psychology (OR=2.754); the ones of partial epileptic seizures are family history risk factors (OR=12.237), the history of febrile convulsions (OR=4.878), poorer psychology (OR=4.471), and history of craniocerebral injury(OR=2.906); the risk factors of indefinitive classification ones are the family history of epilepsy(OR=22.238), and history of febrile convulsions (OR=3.665).(3) Genetic mode and heritability analysis of idiopathic epilepsy:①The prevalence for relatives of probands with idiopathic epilepsy is 5.8%o while the control group is 0.6‰. Relative prevalence rate of probands is higher than the control group.②The first degree relatives of the proband with idiopathic epilepsy performs a prevalence rate of 10.6‰, its heritability estimated is 23.02%±5.21%; the second degree relatives' prevalence is 5.0‰and heritability estimated is 9.21%±8.95%. The weighted mean heritability of both is 17.46%±26.87%. Trend test showed that as the increase in series with the relatives, the prevalence of epilepsy showed a significant decreasing tendency(χ2= 29.09, P< 0.05).③In the study of the proband pedigrees, the actual number of cases of epilepsy is not according to the binomial distribution.④The simple segregation ratio of idiopathic epilepsy is 0.034, significantly less than the Mendelian recessive segregation ratio of 0.25. Complex segregation analysis showed that the study accepted Mendelian genetic model (dominant, recessive, additive, and a major gene model) and excluded the general model, non-transmitted model and environment model. But the AIC value of the additive model compared to the other three models is lower, so the additive model is accepted finally.Major study conclusions:(1) Conclusions on the risk factors of epilepsy:①There are many risk factors to the pathogenesis of epilepsy and they are family history of epilepsy, history of febrile seizures, frequent exercise, poorer psychology, and history of craniocerebral injury.②The risk factors of idiopathic epilepsy and secondary epilepsy are different. Family history of epilepsy, history of febrile seizures and poorer psychology are the risk factors of idiopathic epilepsy while history of febrile seizures, history of craniocerebral injury and birth trauma are the risk factors of secondary epilepsy.③The factors of various seizure types of epilepsy are not all the same. Risk factors of Generalized Seizure epilepsy are family history of epilepsy, history of febrile seizures and poorer psychology; the risk factors of partial seizures epilepsy are family history of epilepsy, the history of febrile convulsions, poorer psychology and history of craniocerebral injury; the risk factors of indefinitive classification seizures are the family history of epilepsy and history of febrile convulsions.(2) Conclusions on the genetic epidemiology of idiopathic epilepsy:①In families the incidence of idiopathic epilepsy is not equal, but show a certain degree of clustering.②The estimated heritability of the first degree relatives of the proband is 23.02%±5.21% and that of the second degree relatives is 9.21%±8.95%. The weighted mean heritability of both is 17.46%±26.87%.③The genetic model of the idiopathic epilepsy is not consistent with single-gene inheritance but polygenic inheritance.