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Supplemental material, sj-pdf-1-pmt-10.1177_87551225221097619 for The Role of Clinical Pharmacist in Pediatrics’ Adherence to Antiepileptic Drugs by Suha Jarad, Amal Akour, Wael H. Khreisat, Afrah K. Elshammari and Saba Madae’en in Journal of Pharmacy Technology

Supplemental material, sj-pdf-2-pmt-10.1177_87551225221097619 for The Role of Clinical Pharmacist in Pediatrics’ Adherence to Antiepileptic Drugs by Suha Jarad, Amal Akour, Wael H. Khreisat, Afrah K. Elshammari and Saba Madae’en in Journal of Pharmacy Technology

Laith N AL-Eitan,1,2 Islam M Al-Dalala,3 Afrah K Elshammari,4 Wael H Khreisat,4 Aseel F Nimiri,4 Adan H Alnaamneh,1 Hanan A Aljamal,1 Mansour A Alghamdi5,6 1Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Blood Banking, King Hussein Medical Centre, Royal Medical Services, Amman, Jordan; 4Queen Rania Hospital for Children, King Hussein Medical Center, Royal Medical Services, Amman, Jordan; 5Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia; 6Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi ArabiaCorrespondence: Laith N AL-EitanJordan University of Science and Technology, P.O. Box 3030, Irbid 22110, JordanTel +962-2-7201000 Ext.:23464Fax +962-2-7201071Email lneitan@just.eduPurpose: The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients.Patients and Methods: A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis.Results: The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness.Conclusion: Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).Keywords: pharmacogenetics, anti-epileptic drugs, generalized epilepsy, focal epilepsy, pharmacotherapy, Jordan

Laith N AL-Eitan1,2, Islam M Al-Dalalah1, Mohamed M Mustafa3, Mansour A Alghamdi4, Afrah K Elshammari5, Wael H Khreisat5, Mohammed N Al-Quasmi6, Hanan A Aljamal1 1Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Neuroscience, Jordan University of Science and Technology, Irbid, Jordan; 4Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia; 5Department of Pediatric Neurology, Queen Rania Hospital for Children, King Hussein Medical Center, Royal Medical Services, Amman, Jordan; 6Department of Medical Laboratory, King Abdullah University Hospital, Irbid, JordanCorrespondence: Laith N AL-EitanJordan University of Science and Technology, P.O. Box 3030, Irbid 22110, JordanTel +962 2 720 1000 Ext.:23464Fax +962 2 720 1071Email lneitan@just.edu.joBackground: A total of 50 million persons were diagnosed worldwide with epilepsy. One-third of them are experiencing debilitating seizures despite optimum anti‐epileptic drugs (AEDs) treatment. Several studies have suggested that CYP3A5, CHRM2, and ZNF498 influence the pharmacokinetics of AEDs. Therefore, the severity of the disease as well as the degree of response to the AEDs could be affected by the genetic polymorphisms within these genes.Objectives: In this study, we assessed the effect of certain single nucleotide polymorphisms (SNPs) within CYP3A5, CHRM2, and ZNF498 genes on the susceptibility to develop epilepsy and the responsiveness to AEDs treatment.Methods: A case–control and pharmacogenetic study was conducted on samples of 299 healthy individuals in addition to 296 epileptic patients. Genotypic, allelic, and clinical data association were performed for the selected polymorphisms within the (rs324649, rs420817, rs15524, and rs1859690) in the Jordanian population.Results: The analysis revealed no significant association of the investigated SNPs with epilepsy in general, partial and generalized epilepsy as well as drug responsiveness. CYP3A5 and ZNF498 were associated with family history (P=0.003 and P=0.002, respectively) and the classification of epilepsy for the ZNF498 variant (P=0.009). On the other hand, CHRM2 was not linked to either disease severity or treatment responsiveness.Conclusion: Our results failed to confirm the association of CYP3A5, ZNF498, and CHRM2 variants with either disease development or treatment response. Clinical pharmacogenetic studies may contribute to treatment personalization, appropriate drug dose selection, minimizing drug adverse reactions, increasing drug efficacy, and reducing the costive burdens.Keywords: epilepsy, seizures, cytochrome P-450 CYP3A, pharmacogenetics, humans, anti-epileptic drugs

Laith N AL-Eitan,1,2 Islam M Al-Dalalah,1 Mohamed M Mustafa,3 Mansour A Alghamdi,4 Afrah K Elshammari,5 Wael H Khreisat,5 Hanan A Aljamal11Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Neuroscience, Jordan University of Science and Technology, Irbid, Jordan; 4College of Medicine, King Khalid University, Abha, Saudi Arabia; 5Queen Rania Hospital for Children, King Hussein Medical Center, Royal Medical Services, Amman, JordanBackground: Epilepsy is one of the most common neurological diseases with unclear etiology where its genetic background and treatment regime still need further exploration.Objectives: This study designed to evaluate the pharmacogenomics of MTHFR and ABCC2 genes, and their association with epilepsy susceptibility among Jordanian population.Methods: A case-control study was conducted on Jordanian cohort of 296 epileptic patients and 299 healthy individuals. Custom platform array was used to genotype the genetic polymorphisms within MTHFR (rs1801133) and ABCC2 (rs717620, rs3740066, rs2273697) genes.Results: This study revealed a significant genetic association of MTHFR rs1801133 polymorphism with susceptibility to generalized in general and generalized tonic-clonic epilepsy (GTCE)(p=0.018 and 0.01, respectively). Regarding ABCC2 gene, rs717620 was of linkage with generalized and GTCE subtypes (p=0.045 and 0.048, respectively), while rs717620 was associated with poor responder patients (p=0.036) with no linkage of the ABCC2 haplotypes.Conclusions: MTHFR and ABCC2 polymorphisms showed an association with either epilepsy types in general or subtypes and treatment response among Jordanian population. This study also suggested that these gene polymorphisms have an important role in epilepsy development and drug effectiveness and could be of a great impact in the era of epilepsy diagnosis and treatment.Keywords: methylenetetrahydrofolate reductase deficiency, epilepsy, pharmacogenetics, tonic- clonic epilepsy, psychotic disorders