Role of CYP2C9 polymorphism in phenytoin-related metabolic abnormalities and subclinical atherosclerosis in young adult epileptic patients

Phabphal, Kanitpong; Geater, Alan; Limapichart, Kitti; Sathirapanya, Pornchai; Setthawatcharawanich, Suwanna

doi:10.1016/j.seizure.2012.10.013

Cited by 10 publications

(7 citation statements)

References 22 publications

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“…All four variants were inherited from his father who was also diagnosed with CAE. EFHC1, CYP2C9 , and RYR2 genes are known to be implicated in epilepsy454647. KCNN4 encodes a member of calcium-activated potassium channels.…”

Section: Resultsmentioning

confidence: 99%

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Wang

Rao

et al. 2017

Sci Rep

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Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children. Here we conducted a targeted exome-sequencing of 63 trios of Chinese epilepsy families using a custom-designed NGS panel that covers 412 known and candidate genes for epilepsy. We identified pathogenic and likely pathogenic variants in 15 of 63 (23.8%) families in known epilepsy genes including SCN1A, CDKL5, STXBP1, CHD2, SCN3A, SCN9A, TSC2, MBD5, POLG and EFHC1. More importantly, we identified likely pathologic variants in several novel candidate genes such as GABRE, MYH1, and CLCN6. Our results provide the evidence supporting the application of custom-designed NGS panel in clinic and indicate a conserved genetic susceptibility for epilepsy between Chinese and Caucasian children.

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Section: Resultsmentioning

confidence: 99%

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Wang

Rao

et al. 2017

Sci Rep

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“… 39 Previous studies found that CYP2C9 gene polymorphisms are associated with serum TC and LDL-c levels in young adult patients with epilepsy. 12 In humans, the CYP2C19 gene expression level is about 10% of the CYP2C9 gene, but these two genes have 91.2% sequence uniformity. 40 Recently, studies have found that EETs and CYP2C19 were upregulated in triple-negative breast cancer (TNBC) tumors, which correspond to the fatty acid binding proteins, adipocyte signaling, and metastasis-related processes, which preliminarily confirmed the role of CYP2C19 gene’s endogenous metabolic regulation.…”

Section: Discussionmentioning

confidence: 99%

Association between CYP2C19 gene polymorphisms and lipid metabolism in Chinese patients with ischemic stroke

et al. 2020

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Objective The CYP2C19 genetic variation may be involved in the development of atherosclerotic cardiovascular disease (ASCVD). Serum lipid levels are important risk factors for ASCVD, but the effect of the CYP2C19 gene on serum lipid metabolism remains unclear. This retrospective cohort study investigated the relationship between the CYP2C19 gene polymorphism and serum lipid levels in patients with ischemic stroke (IS). Methods IS patients (n = 230) and control subjects (n = 100) were enrolled. All patients were diagnosed with IS via clinical manifestations and brain magnetic resonance imaging. All patients were genotyped. Results Triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and apolipoprotein B (ApoB) levels were significantly higher and high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A1 (ApoA1) levels were significantly lower in the IS group compared with the control group. Lower ApoA1 levels and higher ApoB levels were significant predictive factors for IS. Patients with higher ApoB levels had a higher risk of IS recurrence. Compared with extensive metabolizers, intermediate and poor CYP2C19 metabolizers had a higher risk of IS recurrence. Conclusions Our study indicates CYP2C19 gene polymorphisms are related to lipid metabolism in patients with IS. IS patients who are poor CYP2C19 metabolizers may have a higher risk of disease recurrence.

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“…Variations within the CYP2C9 gene have also shown associations with phenytoin-related adverse reactions. Phenytoin is primarily metabolized to its inactive form by CYP2C9, and alleles that result in decreased enzymatic activity, specifically CYP2C9*2 and *3 , have been linked with increased phenytoin concentrations [135-138] and an increased risk for neurological toxicities [139, 140] and cutaneous adverse drug reactions [133, 141]. Consideration of both HLA-B*15:02 and CYP2C9*2 and *3 may be important in any future clinical pre-treatment screening programs.…”

Section: Important Variantsmentioning

confidence: 99%

PharmGKB summary

Barbarino

Kroetz²,

Klein³

et al. 2015

Pharmacogenetics and Genomics

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Role of CYP2C9 polymorphism in phenytoin-related metabolic abnormalities and subclinical atherosclerosis in young adult epileptic patients

Abstract: Our study indicates that young epileptic patients with the CYP2C9 polymorphism gene have a low risk of subclinical atherosclerosis.

Cited by 10 publications

References 22 publications

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Association between CYP2C19 gene polymorphisms and lipid metabolism in Chinese patients with ischemic stroke

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