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Meta-Analysis
. 2018 Dec 18;38(6):BSR20181654.
doi: 10.1042/BSR20181654. Print 2018 Dec 21.

Association between SCN1A polymorphism rs3812718 and valproic acid resistance in epilepsy children: a case-control study and meta-analysis

Zhi Jian Wang  1 , Jie Chen  2 , Hai Liang Chen  1 , Lin Yan Zhang  1 , Duo Xu  1 , Wen Ting Jiang  1
Affiliations
Meta-Analysis

Association between SCN1A polymorphism rs3812718 and valproic acid resistance in epilepsy children: a case-control study and meta-analysis

Zhi Jian Wang et al. Biosci Rep. .

Abstract

Resistance to valproic acid (VPA), a first-line antiepileptic drug (AED), is occurring at an alarming rate, particularly in children. Signal nucleotide polymorphisms are considered crucial in this process. Therefore, we investigated whether the SCN1A polymorphism rs3812718 could be associated with VPA resistance. A total of 231 children with epilepsy who were solely administered VPA were enrolled. DNA was extracted from the peripheral blood samples and was genotyped by the Mass Array method. Furthermore, a meta-analysis was conducted between the drug responsive and resistant patients who were exposed to voltage-gated sodium channels. Results revealed that the TT genotype was associated with a higher risk of developing drug resistance (OR = 2.636, 95% CI 1.08-6.433, P = 0.033). After adjusting for the risk factors, a significant difference was still observed between the responsive and resistant groups (OR = 2.861, 95% CI 1.141-7.174, P = 0.025). Moreover, the recessive model was associated with a decreased drug resistance (OR = 0.402, 95% CI 0.167-0.968, P = 0.042) after correcting the risk factors. Meta-analysis of nine studies revealed similar results. In conclusion, our results proved that the rs3812718 TT genotype was associated with a high risk of developing drug resistance, and the recessive model could decrease the risk of VPA resistance.

Keywords: Drug resistant; Epilepsy; Meta-analysis; SCN1A; Single Nucleotide Polymorphism; Valproic acid.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. The forest plot of the SCN1A rs3812718 between drug resistant and responsive group under recessive model
Figure 2
Figure 2. The evaluation of the publication bias under recessive model
A is the Begg’s funner plot. B is the sensitivity analysis.
See this image and copyright information in PMC

References

    1. Brodie M.J. (2016) Pharmacological treatment of drug-resistant epilepsy in adults: a practical guide. Curr. Neurol. Neurosci. Rep. 16, 82 10.1007/s11910-016-0678-x - DOI - PubMed
    1. Zhu M.M., Li H.L., Shi L.H., Chen X.P., Luo J. and Zhang Z.L. (2017) The pharmacogenomics of valproic acid. J. Hum. Genet. 62, 1009–1014 10.1038/jhg.2017.91 - DOI - PubMed
    1. Abo E.F.W., Abd E.N.S., Habib M.S., ALrefai A.A. and Kasemy Z.A. (2016) The potential implication of SCN1A and CYP3A5 genetic variants on antiepileptic drug resistance among Egyptian epileptic children. Seizure 41, 75–80 10.1016/j.seizure.2016.07.005 - DOI - PubMed
    1. Thompson C.H., Kahlig K.M. and George A.J. (2011) SCN1A splice variants exhibit divergent sensitivity to commonly used antiepileptic drugs. Epilepsia 52, 1000–1009 10.1111/j.1528-1167.2011.03040.x - DOI - PMC - PubMed
    1. Heinzen E.L., Yoon W., Tate S.K., Sen A., Wood N.W., Sisodiya S.M.. et al. (2007) Nova2 interacts with a cis-acting polymorphism to influence the proportions of drug-responsive splice variants of SCN1A. Am. J. Hum. Genet. 80, 876–883 10.1086/516650 - DOI - PMC - PubMed

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