An association analysis of reelin gene (RELN) polymorphisms with childhood epilepsy in eastern Indian population from West Bengal

Abstract

Epilepsy is a common neurological condition characterized by unprovoked seizure attacks. Early brain developmental abnormalities involving neuronal migration and lamination are implicated in childhood epilepsy. Reelin, a neuronal-signaling molecule plays a crucial role in these migratory processes. Therefore, reelin gene (RELN), which is located on human chromosome 7q22 is considered as a potential candidate gene for childhood epilepsy. In this study, we recruited 63 patients with childhood-onset epilepsy and 103 healthy controls from West Bengal in India. Genomic DNA isolated from leukocytes of cases and control individuals were used for genotyping analysis of 16 markers of RELN. Case-control analysis revealed significant over-representation of G/C and (G/C+C/C) genotypes, and C allele of exon 22 G/C marker (rs362691) in cases as compared to controls. Pair-wise linkage disequilibrium analysis demonstrated two separate LD blocks with moderately high D' values in epileptic cases. Based on these data, we have carried out haplotype case-control analysis. Even though we found over-representation of A-C haplotype of intron 12 A/C/exon 22 G/C markers and haplotype combination involving G-allele of exon 22 marker in cases and controls, respectively, the overall test was not significant. LD in this region involving this marker was also more robust in epileptic cases. Taken together, the results provide possible evidences for association of exon 22 G/C marker or any marker in the vicinity, which is in LD with this marker with epilepsy in the West Bengal population. Further investigations involving higher sample sizes are warranted to validate the present finding.

Fig. 1

Graphical representation of pair-wise LD in epileptic cases and controls from West Bengal. We have measured the extent of linkage disequilibrium (LD) between pairs of markers of RELN using GOLD program. Physical distance between the markers were plotted along X and Y axis of the graph. The magnitude of LD was measured according to the color scheme. The bright red (top) and deep blue (bottom) colors at the two extreme end of the color coding scheme (vertical bar) depicted strongest and weakest LD measures between the pair of markers, respectively, whereas in-between colors of various shades of yellow, green and blue demonstrate intermediate LD values. Panels (a) and (b) depicts the graphical representation of LD measurement between pair of markers of RELN in epileptic cases and controls from West Bengal, respectively. (Color figure online)