Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability

Transgenic mice lacking a functional 5-HT2c receptor gene are extremely sus ceptible to audiogenic seizures, suggesting that 5-HT2c receptors mediate i nhibition of neuronal network. excitability, The present association study tested the hypothesis that a Cys23Ser substitution polymorphism within the human 5-HT2c receptor gene modulates neuronal excitability, Genotypes of th e: Gys23Ser polymorphism were assessed in 454 subjects of German descent, c omprising: 1) 93 severely affected alcohol-dependent males with a history o f alcohol withdrawal seizure or delirium, 2) 119 patients affected by an id iopathic generalized epilepsy,and 3) 242 controls. Both sexes were analyzed separately because of the X-chromosomal location of the 5-HT2c receptor ge ne,The allele frequencies of the Cys23Ser variants did not differ significa ntly between the controls and either the severely affected alcohol-dependen t males (P + 0.34), or patients with idiopathic generalized epilepsy (P > 0 .57). Our results suggest that the common Cys23Ser substitution polymorphis m of the: human 5-HT2c receptor gene does not confer susceptibility to neur onal hyperexcitability in either idiopathic generalized epilepsy or alcohol withdrawal seizure or delirium. (C) 1999 Wiley-Liss, Inc.