Association Study of TRPC4 as a Candidate Gene for Generalized Epilepsy with Photosensitivity

• Published in: Neuromolecular medicine 2010-09, Vol.12 (3), p.292-299
• Main Authors: von Spiczak, Sarah, Muhle, Hiltrud, Helbig, Ingo, de Kovel, Carolien G. F., Hampe, Jochen, Gaus, Verena, Koeleman, Bobby P. C., Lindhout, Dick, Schreiber, Stefan, Sander, Thomas, Stephani, Ulrich
• Format: Article
• Language: English
• Subjects: Base Sequence; Biomedical and Life Sciences; Biomedicine; Epilepsy, Generalized - genetics; Epilepsy, Reflex - genetics; Genetic Predisposition to Disease; Genotype; Haplotypes; Internal Medicine; Neurology; Neurosciences; Original Paper; Photic Stimulation; Polymorphism, Single Nucleotide; TRPC Cation Channels - genetics
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-010-8122-x

Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the TRPC4 gene. Thirty-five single nucleotide polymorphisms (SNP) within TRPC4 were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I–IV; n  = 273), a narrow model of affectedness (PPR types III and IV; n  = 214) and PPR associated with IGE (PPR/IGE; n  = 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers ( P  = 0.005) and haplotype level ( P  = 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at P