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Association Analysis Of The Genetic Polymorphisms Of CYP2C9/CYP2C19and Phenobarbital Serum Concentration In Hui And Han Patients With Epilepsy

Posted on:2013-11-07Degree:MasterType:Thesis
Country:ChinaCandidate:M S QiFull Text:PDF
GTID:2284330362472507Subject:Neurology
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Background: Epilepsy is a common neurological disorders, and seizures canbe controlled by antiepileptic drugs(AEDs) in patients with epilepsy. When peoplewith epilepsy take AEDs, we found that drug response and efficacy, as well asadverse drug event are variable among different individuals. Some AEDs, such asphenobarbital, are metabolized by cytochrome P450(CYP) isoenzymes, mainlyincluding CYP2C9and CYP2C19. The genetic polymorphisms of CYP2C9andCYP2C19contribute to the pharmacokinetic variability of phenobarbital. Thegenetic polymorphisms of CYP2C9and CYP2C19are variable among differentpopulations, and it means that the activities of CYP may be different amongdifferent ethics. we explore the frequency of polymorphism at CYP2C9*3andCYP2C19*2in Ningxia Hui and Han epileptic patients and compare the singlenucleotide polymorphism(SNPs) between different nations, then study therelationship between the genotypes and the phenobarbital serum concentration inpatients with epilepsy. we can predict phenobarbital serum concentration correctlyand choose appropriate phenobarbital doses to minimize the adverse reactions aspossible.Objective: To investigate the frequency of polymorphism at CYP2C9*3andCYP2C19*2in Hui and Han-nation epileptic patients, then study the relationshipbetween the genotypes and the phenobarbital serum concentration in patients with epilepsy.Materials and methods: The peripheral blood samples of185patients withepilepsy were collected to undergo PCR-RFLP to analysis CYP2C9*3andCYP2C19*2genotypes, then compare SNPs between different nations. RP-HPLCwas used to measure the phenobarbital serum concentration of113patients whoonly take phenobarbital, then standardized by dosage and body weight.Results:1.There were no signifiscant differences both in CYP2C9*3andCYP2C19*2SNPs between Hui and Han groups(both p>0.05).2. The phenobarbital serum concentrations of the CYP2C9*1/*3genotypes were significantly higher than that of the CYP2C9*1/*1(p<0.05).3. The phenobarbital serum concentration of the PM and IM groupwas significantly higher than that of the EM group.Conclusion: Hui and Han groups have CYP2C9*3and CYP2C19*2SNPs,and the SNPs have no signifiscant differences between the two groups. A positivecorrelation exists between the mutant alleles and phenobarbital serumconcentrations.
Keywords/Search Tags:antiepileptic drugs(AEDs), phenobarbital(PB), CYP2C9*3, CYP2C19*2, single nucleotide polymorphism(SNPs)
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