Abstracts

Rationale: We identified a mis-sense single nucleotide polymorphism (SNP) in the Kcnj10 gene that associates with seizure susceptibility in mice (Ferraro et al 2004) and a mis-sense SNP in the human KCNJ10 gene that associates with epilepsy (Buono et al 2004). Supportive evidence for the human association has been documented by two separate groups in independent cohorts (Lenzen et al 2005, Heuser et al 2008). In addition, rare mutations in the KCNJ10 gene have been linked to syndromes that include epilepsy, ataxia, cognitive impairment and renal dysfunction (Bockenhauer et al 2009, Scholl et al 2009). We now provide genotype data on 8 SNPS distributed across the KCNJ10 region, including the adjacent genes, KCNJ9, IGSF8 and PIGM, in a population of epilepsy patients (N = 752) compared to controls (N = 317) in which haplotype analysis continues to support a role for the KCNJ10 locus in human epilepsy. Methods: The cohort represents a population of Caucasian patients with common forms of epilepsy as studied previously in our lab (Buono et al., 2004). Forms of epilepsy collected include idiopathic generalized epilepsies (juvenile myoclonic epilepsy, juvenile absence epilepsy and childhood absence epilepsy, N = 435) and partial epilepsies (temporal lobe epilepsy and cryptogenic focal epilepsy, N = 317). No symptomatic forms of epilepsy are included and inclusion/exclusion criteria have been published previously (Buono et al., 2004). Cocaphase haplotype analysis was conducted using a 4-marker sliding window across a series of 8 SNPs in KCNJ10, KCNJ9, PIGM and IGSF8 genes. The following 8 SNPs were included in the analysis: 1) rs12409352 (PIGM); 2) rs1130183 (KCNJ10); 3) rs12122979 (KCNJ10); 4) rs7512587 (KCNJ10); 5) rs2737703 (KCNJ9); 6) rs2753268 (KCNJ9); 7) rs2295621 (IGSF8); 8) rs2369406 (IGSF8). Results: Our results show a specific haplotype including markers 4, 5, 6 and 7 that is highly associated with epilepsy (p = 0.003, OR 3.1). Conclusions: These data suggest that the region including KCNJ10 and KCNJ9 harbors variation that increases risk for epilepsy. The same alleles have been implicated in the study by Heuser et al. (2008). We conclude that these data provide further support for a role of the inward rectifying potassium ion channels KCNJ10 and possibly KCNJ9 in human epilepsy.