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The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies
OBJECTIVE: Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1) polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive. METHODS: The Pubmed, Embase, W...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376792/ https://www.ncbi.nlm.nih.gov/pubmed/25816099 http://dx.doi.org/10.1371/journal.pone.0122043 |
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author | Li, Hui Wang, Bing Chang, Cheng Wu, Minghua Xu, Yun Jiang, Yajun |
author_facet | Li, Hui Wang, Bing Chang, Cheng Wu, Minghua Xu, Yun Jiang, Yajun |
author_sort | Li, Hui |
collection | PubMed |
description | OBJECTIVE: Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1) polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive. METHODS: The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity. RESULTS: A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy) were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T), we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01). However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians), no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable. CONCLUSION: In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians. |
format | Online Article Text |
id | pubmed-4376792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43767922015-04-04 The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies Li, Hui Wang, Bing Chang, Cheng Wu, Minghua Xu, Yun Jiang, Yajun PLoS One Research Article OBJECTIVE: Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1) polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive. METHODS: The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity. RESULTS: A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy) were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T), we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01). However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians), no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable. CONCLUSION: In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians. Public Library of Science 2015-03-27 /pmc/articles/PMC4376792/ /pubmed/25816099 http://dx.doi.org/10.1371/journal.pone.0122043 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Li, Hui Wang, Bing Chang, Cheng Wu, Minghua Xu, Yun Jiang, Yajun The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies |
title | The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies |
title_full | The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies |
title_fullStr | The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies |
title_full_unstemmed | The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies |
title_short | The Roles of Variants in Human Multidrug Resistance (MDR1) Gene and Their Haplotypes on Antiepileptic Drugs Response: A Meta-Analysis of 57 Studies |
title_sort | roles of variants in human multidrug resistance (mdr1) gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376792/ https://www.ncbi.nlm.nih.gov/pubmed/25816099 http://dx.doi.org/10.1371/journal.pone.0122043 |
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