Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications
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 respon...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023111509 |
| _version_ | 1797336871101005824 |
|---|---|
| author | Shitao Wang Zongyou Li Zhibo Gao Mengen Zhang Feng Rao Jinghong Lu Hui Xu Zhenrong Xie XiangQian Ding |
| author_facet | Shitao Wang Zongyou Li Zhibo Gao Mengen Zhang Feng Rao Jinghong Lu Hui Xu Zhenrong Xie XiangQian Ding |
| author_sort | Shitao Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T09:01:11Z |
| format | Article |
| id | doaj.art-0df862e5bb244c0f95f8913c233d73cd |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T09:01:11Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-0df862e5bb244c0f95f8913c233d73cd2024-02-01T06:34:13ZengElsevierHeliyon2405-84402024-01-01101e23942Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medicationsShitao Wang0Zongyou Li1Zhibo Gao2Mengen Zhang3Feng Rao4Jinghong Lu5Hui Xu6Zhenrong Xie7XiangQian Ding8Department of Neurology, Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang 236000, Anhui, China; Corresponding author.Department of Neurology, Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang 236000, Anhui, ChinaDepartment of neurosurgery, Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang 236000, Anhui, ChinaDepartment of Neurology, Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang 236000, Anhui, ChinaDepartment of Neurology, Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang 236000, Anhui, ChinaDepartment of Neurology, Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang 236000, Anhui, ChinaDepartment of Neurology, Affiliated Fuyang People's Hospital of Anhui Medical University, Fuyang 236000, Anhui, ChinaThe Medical Biobank, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, ChinaDepartment of neurosurgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, ChinaBackground: 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.http://www.sciencedirect.com/science/article/pii/S2405844023111509EpilepsyTherapyRs717620ABCC2Polymorphism |
| spellingShingle | Shitao Wang Zongyou Li Zhibo Gao Mengen Zhang Feng Rao Jinghong Lu Hui Xu Zhenrong Xie XiangQian Ding Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications Heliyon Epilepsy Therapy Rs717620 ABCC2 Polymorphism |
| title | Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications |
| title_full | Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications |
| title_fullStr | Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications |
| title_full_unstemmed | Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications |
| title_short | Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications |
| title_sort | integrative analysis of rs717620 polymorphism in therapeutic response to anti seizure medications |
| topic | Epilepsy Therapy Rs717620 ABCC2 Polymorphism |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023111509 |
| work_keys_str_mv | AT shitaowang integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT zongyouli integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT zhibogao integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT mengenzhang integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT fengrao integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT jinghonglu integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT huixu integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT zhenrongxie integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications AT xiangqianding integrativeanalysisofrs717620polymorphismintherapeuticresponsetoantiseizuremedications |