HUMAN PRION PROTEIN GENE VARIANT ALLELE IS ASSOCIATED WITH MESIAL TEMPORAL LOBE EPILEPSY AND PREDICTS ITS SURGICAL OUTCOME
Abstract number :
1.203
Submission category :
Year :
2003
Submission ID :
3656
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Roger Walz, Rosa M.R.P.S. Castro, Tonicarlo R. Velasco, Veriano Alexandre, Jr., Marilene H. Lopes, Jo[atilde]o P. Leite, Ant[ocirc]nio C. Santos, Jo[atilde]o A. Assirati, Jr., Lauro Wichert-Ana, Vera C. Terra-Bustamante, Marino M. Bianchin, Paulo C. Macia
Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrPc) gene ([italic]Prnp[/italic]) enhances neuronal excitability of the hippocampus [ldquo]in vitro[rdquo] and sensitivity to seizure [ldquo]in vivo[rdquo] indicating that PrPc might be related to epilepsy. We investigated the association among [italic]Prnp[/italic] variant alleles and the surgical outcome of MTLE-HS patients.
[italic]Prnp[/italic] coding sequence of DNA from leucocytes of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls which were similar according to sex, age and ethnicity (n=180). The presence of [italic]Prnp [/italic]variant alleles was correlated with sex, ethnicity, age at surgery, age of epilepsy onset (recurrent seizures), the duration of epilepsy, positive history for initial precipitating insult, epilepsy duration until surgery, positive family history of seizures in the first-degree offspring, monthly complex partial seizure frequency impairing awareness in the year before surgery, distribution of interictal spikes, neuroimaging, side of surgery and surgical outcome. Surgical outcome was analysed by Kaplan-Meier curve followed by cox proportional hazards model to identify independent risk factors for having seizures seizures after surgery after surgery.
A variant allele at position 171 (Asn[rarr]Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients ([italic]p[/italic][lt]0.0001). The [italic]Prnp[/italic] genotypes were not correlated with any clinical and presurgical investigated data. However, patients carrying Asn171Ser variant had five times greater chance to remain with seizures after temporal lobectomy (CI 95% 1.65 to 17.33, [italic]p[/italic]=0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure-free Cox proportional hazards model was applied to identify independent risk factors for having seizures after surgery in comparison to 68.2% of those carrying Asn171Ser ([italic]p=[/italic]0.005).
[italic]Prnp[/italic] variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and independently predicts their surgical outcome. The results suggests that [italic]Prnp[/italic] variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.
[Supported by: grants from FAPESP (99/07124-8, 98/143352) and FAEPA-HC.]