Association between EPHX1 polymorphisms and carbamazepine metabolism in epilepsy: a meta-analysis

Zhao, Gui-Xin; Shen, Ming-Li; Zhang, Zheng; Wang, Ping; Xie, Chun-Xiang; He, Gong-Hao

doi:10.1007/s11096-019-00919-y

Cited by 12 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MJS metabolism of anticoagulant and anticonvulsant medicines, such as mephenytoin, warfarin, tolbutamide, and phenytoin may be compromised due to the pathogenic mutations in CYP2C19 (rs4244285) (Arici and Özhan 2017) and antiepileptic carbamazepine metabolism affected by rs1051740 polymorphism (which was predicted to be deleterious by all the three previously described functional impact prediction tools) in the gene EPHX1 (Zhao et al 2019). Moreover, substitution of the valine to alanine found in MJS in position 174 of the SLCO1B1 gene (rs4149056), which was also confirmed by multiple tools to be deleterious, is known to reduce uptake and transport activity of cholesterollowering drugs such as simvastatin, pravastatin, pitavastatin, and fexofenadine (Voora et al 2009) which increases the risk of statin-induced myopathy (Link et al 2008).…”

Section: Functional Classification Of the Variantsmentioning

confidence: 99%

Decoding a highly mixed Kazakh genome

et al. 2020

View full text Add to dashboard Cite

We provide a Kazakh whole genome sequence (MJS) and analyses with the largest comparative Kazakh genomic data available to date. We found 102,240 novel SNVs and a high level of heterozygosity. ADMIXTURE analysis confirmed a significant proportion of variations in this individual coming from all continents except Africa and Oceania. A principal component analysis showed neighboring Kalmyk, Uzbek, and Kyrgyz populations to have the strongest resemblance to the MJS genome which reflects fairly recent Kazakh history. MJS's mitochondrial haplogroup, J1c2, probably represents an early European and Near Eastern influence to Central Asia. This was also supported by the heterozygous SNPs associated with European phenotypic features and strikingly similar Kazakh ancestral composition inferred by ADMIXTURE. Admixture (f3) analysis showed that MJS's genomic signature is best described as a cross between the Neolithic East Asian (Devil's Gate1) and the Bronze Age European (Halberstadt_LBA1) components rather than a contemporary admixture.

show abstract

Section: Functional Classification Of the Variantsmentioning

confidence: 99%

Decoding a highly mixed Kazakh genome

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It was previously reported that genetic variation of drug-metabolizing enzymes could generate the inter-individual differences in the pharmacokinetics and pharmacodynamics of epileptic patients[10-12]. In our recent meta-analysis, it was further proved that EPHX1 polymorphisms (rs1051740 and rs2234922) were significantly associated with concentrations of both CBZ and CBZE and metabolism ratio[13]. However, previous studies regarding the effects of polymorphisms of CYP3A4/3A5 on the pharmacokinetics and pharmacodynamics of CBZ still remain controversial.…”

Section: Introductionmentioning

confidence: 89%

Associations betweenCYP3A4, CYP3A5andSCN1APolymorphisms and Carbamazepine Metabolism in Epilepsy: A Meta-analysis

Zhao

Zhang

Cai³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background and objective: CYP3A4 (rs2242480), CYP3A5 (rs776746) and SCN1A (rs3812718 and rs2298771) gene polymorphisms were previously indicated to be associated with carbamazepine (CBZ) metabolism and resistance in epilepsy. However, previous studies regarding the effects of these polymorphisms still remain controversial. Therefore, we performed a meta-analysis to evaluate whether the four polymorphisms are associated with CBZ metabolism and resistance. Methods: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc and Wan fang Database were searched up to January 2020 for appropriate studies regarding the association of rs2242480, rs776746, rs3812718 and rs2234922 polymorphisms with metabolism and resistance to CBZ. The meta-analysis was conducted by Review Manager 5.3 software. Results: Eighteen studies involving 2574 related epilepsy patients were included. Significant associations between CYP3A4 rs2242480, CYP3A5 rs776746 and SCN1A rs3812718 polymorphisms and plasma concentrations of CBZ were observed. Additionally, SCN1A rs3812718 polymorphism was significantly associated with CBZ resistance. However, no association was observed between SCN1A rs2298771 polymorphism and metabolism and resistance to CBZ. Conclusion: The CYP3A4 rs2242480, CYP3A5 rs776746 and SCN1A rs3812718 polymorphisms may play important roles in metabolism and resistance to CBZ, while SCN1A rs2298771 polymorphism is not associated with CBZ in epilepsy. These findings would improve the individualized therapy of epileptic patients in clinics.

show abstract

“…Moreover, several association studies between this polymorphisms and CBZ metabolism or plasma level of CBZ exhibited controversial findings. 28,29 For example, it was shown that patients carrying the CC genotype of EPHX1 on were associated with a lower plasma concentration of CBZ compared with the CT or TT genotypes. 30 By contrast, some studies found that this polymorphism had no significant influence on plasma concentration of CBZ and CBZ-10,-11-epoxide.…”

Section: Introductionmentioning

confidence: 99%

“…These data suggested that the influence of the rs1051740 of EPHX1 on enzyme activity may be substrate‐specific. Moreover, several association studies between this polymorphisms and CBZ metabolism or plasma level of CBZ exhibited controversial findings 28,29 . For example, it was shown that patients carrying the CC genotype of EPHX1 on were associated with a lower plasma concentration of CBZ compared with the CT or TT genotypes 30 .…”

Section: Introductionmentioning

confidence: 99%

“…The CBZ 10,11-epoxide is transformed by mEH, which is encoded by the EPHX gene, to an inactive metabolite, the CBZ-10,11-diol. Although the rs1051740 of EPHX1 could affect the mEH activity and CBZ and CBZ 10,11-epoxide plasma concentrations [25][26][27][28][29][30][31][32]. The study about the association of EPHX1 polymorphism and CBZ-induced SCARs is very limited.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Genetic variants associated with severe cutaneous adverse drug reactions induced by carbamazepine

Nakkam

Konyoung

Amornpinyo

et al. 2021

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims Carbamazepine (CBZ) is one of the most common causative drugs of severe cutaneous adverse drug reactions (SCARs) including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms. Although genetic polymorphisms of the human leucocyte antigens (HLA) are well recognized key elements for the susceptibility to CBZ‐induced SCARs, some evidence suggest that polymorphisms of microsomal epoxide hydrolase 1 (EPHX1) may also contribute to the risk of these SCARs. This study investigated the association between the HLA and EPHX1 polymorphisms on CBZ‐induced SCARs in large sample sizes and well‐defined SCARs patients. Methods Ninety‐one CBZ‐induced SCARs Thai patients and 144 CBZ‐tolerant patients were enrolled in the study. The genotypes of HLA‐A, HLA‐B and EPHX1 were determined. Results Only 2 HLA alleles including HLA‐B*15:02 and HLA‐A*24:07 were statistically significant association with CBZ‐induced SJS/TEN. The highest risk was observed in patients with HLA‐B*15:02 allele (OR = 44.33, 95% confidence interval = 20.24–97.09, corrected P‐value = 6.80 × 10−29). Moreover, HLA‐B75 serotypes were significantly associated with CBZ‐induced SJS/TEN groups with an odds ratio of 81.00 (95% confidence interval = 32.39–202.56, corrected P‐value = 3.84 × 10−34). There is no association between EPHX1 c.337 T > C polymorphism and all phenotypes of CBZ‐induced SCARs. Conclusion The HLA‐B*15:02 allele is the strongest genetic marker for the prediction of SJS/TEN induced by CBZ in Thai population. Screening for other alleles in the HLA‐B75 serotype increases sensitivity for prediction of a life‐threatening SCARs caused by CBZ.

show abstract

Association between EPHX1 polymorphisms and carbamazepine metabolism in epilepsy: a meta-analysis

Cited by 12 publications

References 33 publications

Decoding a highly mixed Kazakh genome

Decoding a highly mixed Kazakh genome

Associations betweenCYP3A4, CYP3A5andSCN1APolymorphisms and Carbamazepine Metabolism in Epilepsy: A Meta-analysis

Genetic variants associated with severe cutaneous adverse drug reactions induced by carbamazepine

Contact Info

Product

Resources

About