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Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications

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机构: [1]Department of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical University, Fuyang 236000, Anhui, China [2]Department of neurosurgery, Affiliated Fuyang People’s Hospital of Anhui Medical University, Fuyang 236000, Anhui, China [3]The Medical Biobank, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China [4]Department of neurosurgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
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关键词: Epilepsy Therapy Rs717620 ABCC2 Polymorphism

摘要:
Background: Previous studies have shown that the rs717620 polymorphism in ABCC2, the gene encoding multidrug resistance protein 2, influences the therapeutic response to anti-seizure medications (ASMs). However, this result is not consistent, and the mechanism by which rs717620 influences ASM responses is unclear. Aims: The present study evaluated the association between rs717620 genotype and ASM efficacy, and examined the potential mechanisms. Main: methods: We conducted a literature search of five electronic databases, Embase, Medline, Web of Science, China National Knowledge Infrastructure, and Wanfang, to identify relevant studies on response to ASM therapy among rs717620 genotypes. Expression quantitative trait loci analysis and drug-gene interaction analysis were also performed to assess the underlying mechanisms.Key findings: The pooled results for 18 studies revealed a significant association between rs717620 genotype and ASM resistance under the recessive model (TT vs. CT + CC: OR = 1.68, 95 % CI = 1.27-2.21, I2 = 3.1 %). A significant association was also found in the Asian population under the recessive model (TT vs. CT + CC: OR = 1.70, 95 % CI = 1.26-2.29, I2 = 29.3 %). Further analysis revealed that rs717620 regulates the expression of ABCC2 in human brain, while drug-gene interaction analysis suggested that ABCC2 interacts with oxcarbazepine and carbamazepine.Significance: The rs717620 polymorphism influences ASM therapeutic responses by altering brain expression levels of ABCC2.

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大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of Neurology, Affiliated Fuyang People’s Hospital of Anhui Medical University, Fuyang 236000, Anhui, China
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