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The Relation of Multidrug Resistance Gene-1、BDNF Gene Polymorphisms to Childhood Intractable Epileptics and a Systematical Study on Their Quality of Life

Author: WangGuangXin
Tutor: YangZuoCheng
School: Central South University
Course: Pediatrics
Keywords: children intractable epilepsy multidrug resistance genel BDNF gene quality of life scale psychological intervention
CLC: R742.1
Type: PhD thesis
Year: 2007
Downloads: 350
Quote: 0
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Abstract


Epilepsy is a common chronic neural disease,approximately 60% of epileptics had their seizure initially from childhood. 70%~80% of children with epilepsy could be controlled by regular use of antiepileptic drugs, the other 20%~30% of them couldn’t be well controlled, which then be called intractable epilepsy or drug resistance epilepsy. The seizures could not only lead to physical damage, but also conduce to a series of psychosocial problems. For this reason, research on epilepsy, especially intractable epilepsy, is always emphasized by clinicans and scientists.According to basic research,the etiology of intractable epilepsy is complex, it refers to many factors, such as genetic factor, environmental factor, psychosocial factor and so on. The genetic factors include alteration of chromosome number and gene mutation. The gene mutation includes single nucleotide polymorphism and insertion/deletion polymorphism. The study on single nucleotide polymorphism of candidate gene provides one of the approaches to molecular genetics of intractable epilepsy. Multidrug resistance gene-1 that coding drug transporter-P-glycoprotein is discovered first to be related to intractable epilepsy, this gene contains at least 50 single nucleotide polymorphisms and insertion/deletion polymorphisms, of which C3435T polymorphism in exon 26、G2677A/T polymorphism in exon 21 and T-129C polymorphism in the promotor maybe influence expression level of P-glycoprotein. Though a few positive results have been reported, the relationship between C3435T polymorphism、G2677A/T polymorphism and intractable epilepsy has not been confirmed, and that whether T-129C polymorphism is related to intractable epilepsy or not has not been reported yet. The brain-derived neurotrophic factor maybe concerned with intractable epilepsy too, because researches have found high expression of BDNF in the brains of intractable epileptics. Moreover, a novel gene mutation-C270T polymorphism of BDNF gene had been found to affect BDNF expression, so, it is necessory to explore the relationship between this polymorphism and intractable epilepsy.In clinical research, along with transformation of medical mode from biological mode to biological-psychological-social mode, people’s health conception had profoundly changed, tranditional index for evaluating health could not meet the practical demands, the conception of quality of life got its value gradually. The successful treatment for childhood epileptics means not only control of seizure, but also keeping them good psychosocial condition, in short, all around improvement of quality of life. Up to present, there has not been a disease-specific scale designed at home or adapted from abroad for evaluating quality of life of Chinese childhood epileptics, say nothing of systematical research on quality of life of children with intractable epilepsy.This study consists of two parts. First, the molecular genetic mechanism of childhood intractable epilepsy was explored by ways of research on the polymorphisms of multidrug resistance gene 1 and BDNF gene. The second, a disease-specific scale for evaluating quality of life of childhood epileptics, namely, Chinese version of The Child Self-Report Scale of Quality of Life for Children with Epilepsy, was developed, Meanwhile, by application of which, quality of life of Children with intractable epilepsy and psychological intervention effects on them were researched.一、The relationship between two single nucleotide polymorphisms of multidrug resistance gene 1、BDNF gene and childhood intractable epilepsy.Objective: To explore the relationship of two single nucleotide polymorphisms of multidrug resistance gene 1 and BDNF gene to childhood intractable epilepsy. Methods: Two single nucleotide polymorphisms, T-129C polymorphism of multi-drug resistance gene 1 and C270T polymorphism of BDNF gene, were conducted with PCR-restriction fragment length polymorphism analysis. The distribution of genotypes and allele frequencies of two single nucleotide polymorphisms in childhood intractable epilepsy were compared to that in drug respond epilepsy and healthy controls. Results: The distribution of TT genotype and T allele frequencies of multi-drug resistance gene 1 in intractable epilepsy differed significantly from that in drug respond epilepsy and healthy controls(P<0.05); the distribution of CC、CT and TT genotypes and C、T allele frequencies of BDNF gene showed no significant difference between children with intractable epilepsy and that with drug respond epilepsy or healthy controls(P>0.05). Conclusions: The findings suggest that the T-129C polymorphism of multidrug resistance gene 1 maybe associated with childhood intractable epilepsy and may play some role in the etiology of intractable epilepsy, but C270T polymorphism of BDNF gene is not confirmed to be related to childhood intractable epilepsy.二、A systematical study on the quality of life of Children with intractable epilepsy.1. Adaptation and psychometric evaluation of Chinese version of the Child Self-Report Scale of Quality of Life for Children with Epilepsy.Objective: (1) To adapt the Child Self-Report Scale of Quality of Life for Children with Epilepsy, and then develop the Chinese version of the scale. (2) To evaluate the reliability and validity of this scale,. Methods: (1) In the process of adaptation of this scale, such procedure was abided by as: translation, back-translation, cross-cultural adaptation, and pretest. (2) The data got from 32 childhood epileptics who examined by the Chinese version of the Child Self-Report Scale of Quality of Life for Children with Epilepsy were used to evaluate reliability and validity of this scale. Results: (1) A disease-specific scale for evaluating quality of life of childhood epileptics, namely, Chinese version of The Child Self-Report Scale of Quality of Life for Children with Epilepsy, was developed. (2) The evaluation of reliability of this scale show that the test-retest correlation coefficients of total scale and 4 factors is above 0.7, the Cronbach’sαof total scale and 4 factors is above 0.7. (3) The evaluation of validity of this scale show that the content validity is good, as well as internal validity. Conclusions: (1) The Chinese version of The Child Self-Report Scale of Quality of Life for Children with Epilepsy was developed successfully. (2) The reliability and validity of this scale are good enough for meeting psychometric standard.2. Qouality of life of children with intractable epilepsy and the effect of psychological intervention on themObjective: To investigate the quality of life of children with intractable epilepsy and the effect of psychological intervention on them. Methods: 39 children with intractable epilepsy、42 children with drug respond epilepsy、40 healthy children were employed and tested by use of the Chinese version of The Child Self-Report Scale of Quality of Life for Children with Epilepsy. 19 children with intractable epilepsy were tested before and after psychological intervention. Results: Compared with children with drug respond epilepsy and healthy children, children with intractable epilepsy had lower quality of life. After psychological intervention, the quality of life of children with intractable epilepsy improved. Conclusion: Children with intractable epilepsy have worse quality of life, the psychological intervention can improve their quality of life.Above all, this study indicated that:1. the T-129C polymorphism of multi-drug resistance gene 1 maybe associated with childhood intractable epilepsy and play some role in the etiology of intractable epilepsy, but C270T polymorphism of BDNF gene is not found to be related to childhood intractable epilepsy.2. The Chinese version of The Child Self-Report Scale of Quality of Life for Children with Epilepsy was primarily developed successfully. Its psychometric properities are good enough for the use of Chinese children.3. Children with intractable epilepsy have worse quality of life, psychological intervention can improve their quality of life. KEY WORDS children, intractable epilepsy, multidrug resistance genel, BDNF gene, quality of life, scale, psychological intervention

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Brain diseases > Epilepsy
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