Browsing by Author "Banerjee, Moinak"

Now showing 1 - 3 of 3
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    Corpora amylacea deposition in the hippocampus of patients with mesial temporal lobe epilepsy: A new role for an old gene?
    (Indian journal of human genetics, 2011)
    BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is the most common medically refractory epilepsy syndrome in adults, and hippocampal sclerosis (HS) is the most frequently encountered lesion in patients with MTLE. Premature accumulation of corpora amylacea (CoA), which plays an important role in the sequestration of toxic cellular metabolites, is found in the hippocampus of 50-60% of the patients who undergo surgery for medically refractory MTLE-HS. However, the etiopathogenesis and clinical importance of this phenomenon are still uncertain. The ABCB1 gene product P-glycoprotein (P-gp) plays a prominent role as an antiapoptotic factor in addition to its efflux transporter function. ABCB1 polymorphism has been found to be associated with downregulation of P-gp expression. We hypothesized that a similar polymorphism will be found in patients with CoA deposition, as the polymorphism predisposes the hippocampal neuronal and glial cells to seizure-induced excitotoxic damage and CoA formation ensues as a buffer response.MATERIALS AND METHODS: We compared five single nucleotide polymorphisms in the ABCB1 gene Ex06+139C/T (rs1202168), Ex 12 C1236T (rs1128503), Ex 17-76T/A (rs1922242), Ex 21 G2677T/A (rs2032582), Ex26 C3435T (rs1045642) among 46 MTLE-HS patients of south Indian ancestry with and without CoA accumulation.RESULTS: We found that subjects carrying the Ex-76T/A polymorphism (TA genotype) had a five-times higher risk of developing CoA accumulation than subjects without this genotype (Odds ratio 5.0, 95% confidence intervals 1.34-18.55; P = 0.016).CONCLUSION: We speculate that rs1922242 polymorphism results in the downregulation of P-gp function, which predisposes the hippocampal cells to seizure-induced apoptosis, and CoA gets accumulated as a buffer response.
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    Drug resistance in epilepsy and the ABCB1 gene: The clinical perspective.
    (Indian journal of human genetics, 2011)
    Multidrug resistance is one of the most serious problems in the treatment of epilepsy that is likely to have a complex genetic and acquired basis. Various experimental data support the hypothesis that over-expression of antiepileptic drug (AED) transporters may play a pivotal role in drug resistance. Hyyt 6however, key questions concerning their functionality remain unanswered. The idea that P-glycoprotein, encoded by the ABCB1 gene, might mediate at least part of the drug resistance was met with both enthusiasm and skepticism. As in oncology, initial optimism has been clouded subsequently by conflicting results. The first study reporting a positive association between genetic variation in the P-glycoprotein and multidrug-resistant epilepsy was published in 2003. Since then, several other genetic association studies have attempted to verify this result. However, taken overall, the role of P-glycoprotein in drug resistance in epilepsy still remains uncertain. We intend to critically review the inherent problems associated with epilepsy pharmacogenetic studies in general and with ABCB1 polymorphisms studies in particular. The lessons learnt from the ABCB1 studies can help us to guide future association genetics studies to investigate AED resistance, and thereby taking us closer to the cherished dream of personalized AED therapy.
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    Failure to find association between febrile seizures and SCN1A rs3812718 polymorphism in south Indian patients with mesial temporal lobe epilepsy and hippocampal sclerosis.
    (Epilepsy research, 2012)
    We compared the allele and genotype frequencies of SCN1A SNP rs3812718 between patients with MTLE-HS of south Indian ancestry with and without febrile seizures (FS) and with ethnically matched controls. While we observed no significant difference in allele and genotype frequencies of rs3812718 between MTLE-HS patients with and without FS, A allele and AA genotype were overrepresented in MTLE-HS patients when compared to controls. We conclude that in the population studied, although rs3812718 polymorphism increases the susceptibility to MTLE-HS, this is not by increasing the susceptibility to FS.