The effects of R43Q mutation and CYP2C19 polymorphism on clinical correlation in febrile convulsions patients

Introduction: Althoughthe pathogenesis for febrile convulsions (FC) is not known for certain, much emphasis is placed on multifactorial casuality accompanied by high temperature. Recent studies have taken the possibility of genetic susceptibility to the foreground, among others. It has been shown that the mutation R43Q (rs211037) in the Ɣ 2 subunit of the receptor GABA–A leads to the development of FC. In addition, the system cytochrome P450 (CYP450) is an important enzyme system for drug metabolism, and is responsible for the metabolism of antiepileptic drugs. CYP2C9 and CYP2C19 polymorphism is definitive of response to antiepileptic drug treatment, and therefore may provide information on the behaviour of the seizure type. These two entities, both of which play an important part in the genetics of FC, constitute the subject of this study. Materials and Methods:Patients who applied to the clinics of paediatric neurology, paediatric emergency department, and paediatrics and were diagnosed with FC by the paediatric neurologist, whose treatment process or follow up continued between the dates of August 2015 and January 2016 were retrospectively and prospectively included in the study. The study group comprised of 102 patients, and the control group included 96 children who met the above mentioned criteria. The patients were evaluated for EEG and whether they were on medication, as well as being genetically analyzed. Results:Thefindingssuggestthat (i) the presence of FC in thepatienthistory in thecontrolgroupwassignificantwhencomparedtothecontrolgroup (p=0,003); (ii) themajority of FC patients in ourstudywereaged 1-3 (58%), whereastherewerefewerpatientsyoungerthanoneyearorolderthan 3 years (30% and 12%, respectively); (iii) theincidence of FC washigher in boys (1,56/1); (iv) the rate of recurrencewasfoundto be high in FC patients (62%; meanseizurenumber= 2,26); (v) themajority of patientswerediagnosedwithsimple FC (73%), where as complicated FC madeup a muchsmallerportion of thesample (27%); (vi) themajority of patients were subjectedto EEG procedures (92%; 92/100) and in morethanhalf of thecases, abnormal EEG findingswerepresent (56%); (vii) thedruguse rate washigher in patientswithabnormal EEG findings (37/56, %66,7, p=0,001); (viii) thedistributions of R43Q mutationswasfoundto be similar in thestudyandthecontrolgroup (wildtype: 58% studyand 56,3% control; heterozygote: 36% studyand 35% control; andhomozygotemutations: 6% studyand 7,3% control) (p=0,927); (ix) EEG anomalyanddrugusewasfoundto be significant in thestudygroup as regardsclinicaleffects of R43Q mutation (p=0,032 and p=0,021, respectively); (x) all of thepatientswithhomozygous R43Q mutation had abnormal EEG findings as well as higherrates of druguse (5/6, %83,3); (xi) themetabolizerfrequencydistribution of CYP2C19 wasfoundto be similarforbothgroups (rapidmetabolizer in 77% of patientsand 80,2% of controls; intermediatemetabolizer in 22% in patientsand 16,7% of controls; andpoormetabolizer in 1% of patientsand 3% of controls) (p=0,393); and (xii) therewasnosignificantcorrelationbetweenthestudiedvariables (gender, age of first-time FC, number of seizures, type of seizures, familyhistory, relatives, EEG, anddrug) and CYP2C19 polymorphism in the study group (p>0,05). Conclusion: Eventhoughthedistribution of R434Q mutationand CYP2C19 polymorphismwerefoundto be similar in FC patientsandthecontrolgroup, the presence of R43Q mutation in thepatientgroup had a negativecontributiontoabnormal EEGfindingsandthenecessityfordruguse, whichmayindicatetheprognosticimportance of the presence of R43Q mutation in FC patients. Keywords: febrile convulsion, R43Q mutation, CYP2C19 polymorphism, electroencephalography(EEG), drug.