Association of Polymorphism of the Methyl Tetrahydrofolate Reductase (MTHFR) Gene with Anti-Seizure Medication Response in Pediatric Patients in Jeddah, Saudi Arabia

Abstract

Background and Objectives Epilepsy is a chronic brain disease, with inherent and noninherent factors. Although over 20 anti-seizure medications (ASMs) are commercially available, nearly one-third of patients develop drug-resistant epilepsy. We evaluated the association between the clinical features and the methyl tetrahydrofolate (MTHFR) rs1801133 polymorphism and ASMs response among pediatric patients with epilepsy. Materials and Methods This was a multicenter, retrospective, case–control study of 101 children with epilepsy and 59 healthy children in Jeddah. The MTHFR rs1801133 polymorphism was genotyped using the real-time polymerase chain reaction TaqMan Genotyping Assay. Results Among the patients with epilepsy, 56 and 45 showed good and poor responses to ASMs, respectively. No significant genetic association was noted between the single-nucleotide polymorphism (SNP) rs1801133 within the MTHFR gene and the response to ASMs. However, a significant association was noted between reports of drug-induced toxicity and an increase in allele A frequencies. The MTHFR rs1801133 genotype was significantly associated with the development of electrolyte disturbance among good and poor responders to ASMs. Conclusion This is the first pharmacogenetic study of MTHFR in patients with epilepsy in Saudi Arabia that found no significant association between the MTHFR SNP rs1801133 and gene susceptibility and drug responsiveness. A larger sample size is needed for testing gene polymorphisms in the future.

Polymorphisms of the TNF-α, ACE, PAI-1 and MTHFR Genes, and Renal Scarring in Infants with First Febrile Urinary Tract Infection

“…The possible pathogenic mechanism by which Hcy causes damage to blood vessels are: damage to the endothelium of the blood vessels, encouragement and participation in oxidative metabolism of Low Density Lipoprotein (LDL), increased platelets aggregation mediated by thromboxane, inhibition of thrombomodulin expression on cell surface and activation of protein C, improved binding of lipoprotein to fibrin, amplify smooth muscle cell proliferation and collagen accumulation [47][48][49][50]. Studies has suggested a con-Volume 08; Issue 03 J Urol Ren Dis, an open access journal ISSN: 2575-7903 nection between MTHFR gene polymorphisms, especially C677T and A1298C (rs 1801131), and several pathological conditions, including kidney disease, cardiovascular disease, neural tube defects, cancer, inflammatory bowel disease, type 2 diabetes, Down syndrome, headache, epilepsy, Alzheimer's disease, schizophrenia, liver diseases, and numerous chronic diseases and disorders of regulation of embryonic development [51][52][53][54][55][56][57][58].…”