Role of ABCB1 C3435T variant in response to antiepileptic drugs in epilepsy: a review

Over-expression of P-glycoprotein (P-gp), the encoded product of the ATP-binding cassette (ABC), sub-family B, member 1 (ABCB1/MDR1) gene, plays an important role in mediating multidrug resistance to antiepileptic drugs (AEDs) in about 30 of patients with epilepsy. Genetic variation may in part explain inter-individual differences in phenotype-genotype relationships in the pharmacological response of epilepsy patients to AEDs. The synonymous C3435T polymorphism is one of the most common allelic variants in the ABCB1/MDR1 gene, proposed in the causation of refractory epilepsy. Many studies have shown the relationship between C3435T polymorphism and refractoriness to AEDs in epilepsy. However, there is controversy between the findings of various studies, that is, whether ABCB1/MDR1 C3435T gene polymorphism is associated with response to AEDs in epilepsy patients. This review provides a background and discusses the results of investigations on possible confounding factors affecting the interpretation and implementation of association studies in this area

Association of 8q24.21 locus with the risk of colorectal cancer: A systematic review and meta-analysis

Objective: Recent genome-wide association studies of colorectal cancer (CRC) have identified rs6983267 G>T and rs10505477 T>C polymorphisms as key loci in the 8q24 region to be associated with CRC. In the present study, we performed a meta-analysis to determine whether these loci are risk factors for susceptibility to CRC. Materials and Methods: We meta-analyzed the 22 included studies (47,003 cases and 45,754 controls) that evaluated the role of rs6983267 G>T and rs10505477 T>C polymorphisms with CRC risk under alternative genetic models. Results: Meta-analysis of the pooled data showed allelic and genotypic association of the rs6983267 polymorphism with CRC risk in the Asian, European, and Americans with European ancestry. Sub-analysis of the American studies showed negative results in the studies with non-identified ethnicity of the subjects. Meta-analysis of included studies of rs10505477 polymorphism identified allelic and genotypic association with CRC risk in the American subjects. Further meta-analysis of the American studies demonstrated positive results in the studies with non-identified ethnicity of the samples. Conclusion: Our data suggested that the rs6983267 G>T polymorphism is a risk factor for CRC in the Asians, European, and American with the European ancestry populations

MTHFR rs1801133 polymorphism and susceptibility to colorectal cancer in Iranian population: Evidence of a case-control study and meta-analysis

Several studies have investigated whether MTHFR rs1801133 polymorphism contributes to risk of colorectal cancer (CRC), however the results are inconclusive. Aim: The purpose of this study was to investigate this hypothesis in a case-control study and meta-analysis in Iranian population. Materials & methods: This polymorphism was genotyped in the 2421 subjects (46 CRC patients) from Tehran. Meta-analysis was performed for determining the risk effect size of this polymorphism on CRC. Results: Both case-control study and meta-analysis showed no association between rs1801133 and CRC risk or its features. Conclusion: This study failed to identify an association between the rs1801133 and susceptibility to CRC in Iranian population. © 2016 Future Medicine Ltd

SCN1A IVS5N+5 polymorphism and response to sodium valproate: a multicenter study

Aim: Approximately 30 of epilepsy patients do not response to antiepileptic drugs (AEDs). The functional SCN1A IVS5N+5 polymorphism may play a role in response to some AEDs. The purpose of this study was to examine this hypothesis in a cohort study of Malaysian and Hong Kong Chinese epilepsy patients on sodium valproate (VPA) monotherapy and in a meta-analysis. Patients & methods: The SCN1A IVS5N+5 polymorphism was genotyped in 583 Malaysian (84) and Hong Kong Chinese (16) epilepsy patients receiving VPA monotherapy. The related association studies, including the current study, were meta-analyzed by using fixed- and random-effects models under various genetic models. Results: A total of 277 (47.5) and 306 (52.5) patients were VPA nonresponsive and responsive, respectively. Unlike Chinese and Indian patients, Malay nonresponsive patients with idiopathic generalized epilepsy showed significant association, probably caused by the small sample size. Conclusion: The cohort study and meta-analysis did not demonstrate an association between AED responsiveness and this polymorphism. Future studies with a larger sample size of Malays with idiopathic generalized epilepsy are suggested. Original submitted 15 June 2012; Revision submitted 23 July 201. © 2012 Future Medicine Ltd

ABCB1 C3435T polymorphism and the risk of resistance to antiepileptic drugs in epilepsy: a systematic review and meta-analysis.

We failed to show an association between the ABCB1 C3435T polymorphism and the risk of drug-resistance suggesting a revision in contribution of this polymorphism in the multi-drug transporters hypothesis of pharmacoresistance to AEDs in epilepsy

Association between ABCB1 polymorphism and response to sodium valproate treatment in Malaysian epilepsy patients

Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30 of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypeswere assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy