Li Hui, Wang Bing, Chang Cheng, Wu Minghua, Xu Yun, Jiang Yajun
Department of neurology, Jiangsu Province Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.
Department of neurology, Huai'an Hospital of Traditional Chinese Medicine, Jiangsu, China.
PLoS One. 2015 Mar 27;10(3):e0122043. doi: 10.1371/journal.pone.0122043. eCollection 2015.
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.
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.
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.
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.
既往研究报道了三磷酸腺苷结合盒亚家族B成员1（ABCB1，也称为多药耐药基因1，MDR1）多态性及其单倍型与癫痫患者对抗癫痫药物反应风险之间的关联，但结果尚无定论。
检索截至2014年7月15日的PubMed、Embase、Web of Science、中国知网和中国生物医学数据库。根据异质性检验结果，采用固定效应或随机效应模型计算合并比值比（OR）和95%置信区间（CI）。进行Meta回归和Galbraith图分析以探讨可能的异质性。
汇总分析共纳入57项研究，涉及12407例患者（6083例耐药癫痫患者和6324例药物反应性癫痫患者）。对于所有三种多态性（C3435T、G2677T/A和C1236T），我们观察到不同种族间次要等位基因频率范围广泛。在携带C3435T变异T等位基因的白种人患者中，观察到抗癫痫药物耐药风险显著降低，经多重检验校正后仍具有显著性（T vs C：OR=0.83，95%CI=0.71-0.96，p=0.01）。然而，未观察到其他两个变异与抗癫痫药物耐药之间存在显著关联。在ABCB1基因的单倍型方面（所有研究对象均为印度人和亚洲人），未观察到与抗癫痫药物耐药存在显著关联。此外，敏感性分析和累积分析表明，本Meta分析结果稳定。
总之，本Meta分析表明，C3435T变异对抗癫痫药物耐药风险的影响具有种族依赖性，在白种人中具有显著性。此外，有必要在不同种族群体中进一步开展研究，以阐明ABCB1基因单倍型在抗癫痫药物耐药中的可能作用，尤其是在白种人中。
