Association of ABCB1 Gene Polymorphisms and Their Haplotypes with Response to Antiepileptic Drugs: a Systematic Review and Meta-Analysis

Abstract

Our data suggest that the haplotypes of these loci may not be involved in the response to treatment.

Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

“…In a Japanese cohort, even the opposite effect was observed [185]. In the meantime, several meta-analyses comprising 3371 [186], 6673 [187] and 7067 [188] patients have corroborated the missing significant effect between ABCB1 genetics and drug-resistant epilepsy.…”

ABCB1 G2677T/A polymorphism is associated with the risk of drug-resistant epilepsy in Asians

“…However, a series of case-control studies about C3435T polymorphism and resistance to AEDs yielded inconsistent results (Seo et al, 2006;Kim et al, 2006;Shahwan et al, 2007;Hung et al, 2007;Kim et al, 2009;Kwan et al, 2009;Vahab et al, 2009;von Stülpnagel et al, 2009;Grover et al, 2010;Dong et al, 2011;Kumari et al, 2011;Meng et al, 2011;Sayyah et al, 2011;Seven et al, 2014). Further, six meta-analyses (Bournissen et al, 2009;Haerian et al, 2010Haerian et al, , 2011aLeschziner et al, 2007;Nurmohamed et al, 2010;Li et al, 2014) attempted to analyze the findings of these case-control studies, but consistent results were not obtained due to the presence of between-study heterogeneity. Meta-analyses are based on the assumption of etiologic homogeneity across studies, so they may not detect real effects in the presence of between-study heterogeneity.…”

“…Some studies were unable to prove an association between G2677T/A polymorphism and resistance to AEDs (Kim et al, 2006;Shahwan et al, 2007;Vahab et al, 2009;von Stülpnagel et al, 2009;Grover et al, 2010;Dong et al, 2011;Meng et al, 2011;Sayyah et al, 2011;Haerian et al, 2011b;Seven et al, 2014), while others reported a significant association (Hung et al, 2007;Kwan et al, 2009;Subenthiran et al, 2013); moreover, a study from India indicated an association of allele A with drug-resistant epilepsy (Kumari et al, 2011). In addition, a recent meta-analysis involving G2677T/A polymorphism (Haerian et al, 2011a) did not find a significant association between G2677T/A polymorphism and resistance to AEDs in epilepsy (P = 0.07-0.96). However, it should be pointed out that this meta-analysis included two studies that deviated from HWE.…”

“…However, the results of subsequent studies from different countries or populations have been inconsistent. A recent meta-analysis has assessed data published for the ABCB1 haplotype, which includes the G2677T/A polymorphism (Haerian et al, 2011a). This meta-analysis included twelve studies on G2677T/A polymorphism published before August 2010, and found no association between this polymorphism and response to AEDs.…”

P‐glycoprotein (MDR1/ABCB1)

“…Stratification to ethnic groups revealed no further evidence (Bournissen et al, 2009). The most comprehensive meta-analysis was published very recently comprising 7067 patients (Haerian et al, 2011) (Table 12.3).…”