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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.

Li H, Wang B, Chang C, Wu M, Xu Y, Jiang Y - PLoS ONE (2015)

Bottom Line: 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).Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians.

View Article: PubMed Central - PubMed

Affiliation: Department of neurology, Jiangsu Province Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Begg's funnel plots for publication bias test of the association between the ABCB1 C3435T polymorphism and AEDs resistance.No significant funnel asymmetry that could indicate publication bias was observed. The horizontal line in the funnel plot indicates the random-effects summary estimate, and the sloping lines indicate the expected 95% confidence interval for a given standard error, assuming no heterogeneity between studies. Log(OR) is the natural logarithm of the odds ratio. AEDs: antiepileptic drugs; ABCB1: ATP-binding cassette sub-family B member 1.
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pone.0122043.g003: Begg's funnel plots for publication bias test of the association between the ABCB1 C3435T polymorphism and AEDs resistance.No significant funnel asymmetry that could indicate publication bias was observed. The horizontal line in the funnel plot indicates the random-effects summary estimate, and the sloping lines indicate the expected 95% confidence interval for a given standard error, assuming no heterogeneity between studies. Log(OR) is the natural logarithm of the odds ratio. AEDs: antiepileptic drugs; ABCB1: ATP-binding cassette sub-family B member 1.

Mentions: Begg’s funnel plot and Egger’s test were performed to assess potential publication bias of literatures. The shapes of the Begg’s funnel plots did not reveal any signs of obvious asymmetry. (Fig. 3) In addition, Egger’s test did not show statistical significance for publication bias (P = 0.111 for T vs C in C3435T, p = 0.679 for T vs G in G2677T, and p = 0.218 for T vs C in C1236T).


The roles of variants in human multidrug resistance (MDR1) gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.

Li H, Wang B, Chang C, Wu M, Xu Y, Jiang Y - PLoS ONE (2015)

Begg's funnel plots for publication bias test of the association between the ABCB1 C3435T polymorphism and AEDs resistance.No significant funnel asymmetry that could indicate publication bias was observed. The horizontal line in the funnel plot indicates the random-effects summary estimate, and the sloping lines indicate the expected 95% confidence interval for a given standard error, assuming no heterogeneity between studies. Log(OR) is the natural logarithm of the odds ratio. AEDs: antiepileptic drugs; ABCB1: ATP-binding cassette sub-family B member 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376792&req=5

pone.0122043.g003: Begg's funnel plots for publication bias test of the association between the ABCB1 C3435T polymorphism and AEDs resistance.No significant funnel asymmetry that could indicate publication bias was observed. The horizontal line in the funnel plot indicates the random-effects summary estimate, and the sloping lines indicate the expected 95% confidence interval for a given standard error, assuming no heterogeneity between studies. Log(OR) is the natural logarithm of the odds ratio. AEDs: antiepileptic drugs; ABCB1: ATP-binding cassette sub-family B member 1.
Mentions: Begg’s funnel plot and Egger’s test were performed to assess potential publication bias of literatures. The shapes of the Begg’s funnel plots did not reveal any signs of obvious asymmetry. (Fig. 3) In addition, Egger’s test did not show statistical significance for publication bias (P = 0.111 for T vs C in C3435T, p = 0.679 for T vs G in G2677T, and p = 0.218 for T vs C in C1236T).

Bottom Line: 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).Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians.

View Article: PubMed Central - PubMed

Affiliation: Department of neurology, Jiangsu Province Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus