Analysis Of The Single Nucleotide Polymorphisms Of CYP3A4in Southwest Children And Association With Drug Resistance Epilepsy

PARTⅠ ANALYSIS OF THE SINGLE NUCLEOTIDEPOLYMORPHISMS OF CYP3A4IN CHILDREN FROMSOUTHWEST CHINAObjectiveTo investigate the relationship between single nucleotidepolymorphisms (SNPs) of CYP3A4(CYP3A4~*18A, CYP3A4~*1G) andchildren drug resistance epilepsy of China southwest.MethodsTwo hundred and thirty-eight children were enrolled in this study.Among them,83cases were drug-resistant epilepsy (resistance group),87cases were drug effective epilepsy (effective group) and68were normalcontrol (control group). Two single nucleotide polymorphisms ofCYP3A4~*18A and CYP3A4~*1G were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and thenanalyzed the distribution of genotypes and allele frequencies of two SNPS.Results(1) In the investigation, the frequencies of homozygous wild type andheterozygous mutant of CYP3A4~*18A in resistance group were93%and7%respectively, wild-type allele and mutant allele were96%and4%,respectively. The frequencies of homozygous wild-typeof CYP3A4~*18Awere100%both in effective and normal group.The distribution ofgenotypes and allele frequencies of CYP3A4~*18A polymorphism in drugresistance epilepsy were statistical difference compared with those ofeffective (P<0.05)，but no difference compared with normal group(P>0.05).(2) The frequencies of homozygous wild-type of CYP3A4~*1G were47%,45%and50%in resistant, effective and normal group repectively.The heterozygous mutant genotypes were46%,49%and43%, and thehomozygous mutant genotypes were7%,6%, and7%. The frequencies ofwild-type allele were70%,70%, and71%, and that of mutant allele were30%,30%, and29%, respectively. There were no statistical differences inthe distribution of genotypes and allele frequencies of CYP3A4~*1G amongthese three groups (P>0.05). Conclusions(1) The CYP3A4~*18A polymorphism is correlated with drugresistance epilepsy in southwest Chinese children. Detecting CYP3A4~*18A genotype could be one of effective methods to choose antiepilepticdrugs, to judge and predict treatment outcomes.(2) The CYP3A4~*1G polymorphism is not correlated with drugresistance epilepsy in southwest Chinese children. It should be furtherstudy with larger sample numbers. PARTⅡTHE RELATIONSHIP BETWEEN THE SINGLENUCLEOTIDE POLYMORPHISMS OF CYP3A4ANDCHILDREN EPILEPSY DRUG RESISTANTObjective:(1) To analyze the clinical features of drug resistance epilepsy in HanChinese children, to explore the reasons for drug-resistant, to further adjustregime and improve prognosis.(2) To further study the relationship between CYP3A4~*1Gdistribution and different seizure types and etiology in children drugresistant epilepsy, to explore its correlation with drug effective.Methods:83out-patients children with drug resistant epilepsy (resistance group)and87children with drug effective epilepsy (effective group) wereenrolled in Chongqing Children’s Hospital Department of Neurology fromMay2010to August2011. The clinical data, including gender, age, onsetage, seizure type, treatment, and EEG, imaging results, were collected inthe two groups.And then analyzed and compared them between two groups.CYP3A4~*1G genotypes were detected by polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP) method intwo groups. Results:(1) The incidence rate was significantly higher in resistance groupthan in effective group, especially in patients with onset before age1,proportion of focal and uncertain seizures, structural and metabolicetiology, radiographic abnormalities and abnormal EEG.(2) There were no statistical differences in the distribution ofgenotypes and allele frequencies of CYP3A4~*1G polymorphism among thetwo groups of different seizure types (P>0.05).(3) In the patients with hereditary or unknown etiology, thedistribution of genotypes and allele frequencies of CYP3A4~*1Gpolymorphism in the resistance group were significant difference from theeffective group (P<0.05). In the patients with structural or metabolicetiology, the distribution of genotypes and allele frequencies were nosignificant difference in two groups (P>0.05).Conclusions:(1) The clinical features of drug resistance epilepsy in southwestChinese children are early age onset, mostly focal and uncertain seizures,structural or metabolic etiology, abnormal brain imaging results, abnormalEEG changes and failure with multiple AEDs.(2) There is no correlation of CYP3A4~*1G polymorphism with drugresistance epilepsy in different seizure types.(3) Homozygous mutant genotypes of CYP3A4~*1G is possible risk factors in the drug resistance epilepsy with hereditary or unknown etiology.In the patients with hereditary or unknown etiology, detecting CYP3A4~*1G genotypes could be one of effective methods to choose antiepilepticdrugs, to judge and predict treatment outcomes.