Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, Kolkata, India.
Cell Mol Neurobiol. 2011 Jan;31(1):45-56. doi: 10.1007/s10571-010-9551-7. Epub 2010 Aug 10.
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.
癫痫是一种常见的神经系统疾病，其特征是无诱因的癫痫发作。涉及神经元迁移和分层的早期大脑发育异常与儿童癫痫有关。 Reelin 是一种神经元信号分子，在这些迁移过程中起着至关重要的作用。因此，位于人类染色体 7q22 上的 reelin 基因（RELN）被认为是儿童癫痫的候选基因之一。在这项研究中，我们从印度西孟加拉邦招募了 63 名患有儿童期起病的癫痫患者和 103 名健康对照者。从病例和对照个体的白细胞中分离出基因组 DNA，用于 RELN 的 16 个标记的基因分型分析。病例对照分析显示，与对照组相比，病例中 G/C 和（G/C+C/C）基因型以及外显子 22 G/C 标记（rs362691）的 C 等位基因的过度表达。成对连锁不平衡分析表明，在癫痫病例中存在两个具有中等高 D'值的独立 LD 块。基于这些数据，我们进行了单体型病例对照分析。尽管我们发现 12A/C/exon 22G/C 标记的内含子 12A-C 单体型和涉及外显子 22 标记 G 等位基因的单体型组合在病例和对照组中均过度表达，但总体检验不显著。该区域涉及该标记的 LD 在癫痫病例中也更稳健。综上所述，这些结果为exon 22 G/C 标记或与该标记紧密连锁的附近任何标记与西孟加拉邦人群癫痫的关联提供了可能的证据。需要进行涉及更大样本量的进一步研究来验证目前的发现。
