HUMAN CELLULAR PRION PROTEIN GENE VARIANT ALLELES ARE ASSOCIATED WITH INTRACTABLE SYMPTOMATIC EPILEPSIES
Abstract number :
3.087
Submission category :
Year :
2002
Submission ID :
3014
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Roger Walz, Rosa M.R.P.S. Castro, Tonicarlo R. Velasco, Veriano Alexandre Jr., Paulo C. Maciag, Lauro Wichert-Ana, Terra-Bustamante Vera, Jo[atilde]o P. Leite, Regina M.F. Fernandes, Wilson Marques Jr., Hélio R. Machado, Carlos G. Carlotti Jr., Jo[atilde]
RATIONALE: Most cases of medically intractable epilepsy are related to hippocampal sclerosis (HS) and malformations of cortical development (MCD). Molecular defects were mapped in single-gene epilepsies, but HS and most types of MCD have not been regarded as having a major genetic contribution. Deletion of the cellular prion gene (PrPc), enhances neuronal excitability and sensitivity to seizures in mice indicating that PrPc gene might be related to epilepsy.
METHODS: The PrPc gene sequence of peripheral blood cells DNA of 102 patients (mean age 36 years) treated surgically for epilepsy related to HS (N=80) or MCD (N=22) were compared with 172 healthy controls. Statistical analysis was done by Student[prime]s test for independent samples and Fisher[prime]s exact test. The OR and respective 95% CI were also determined.
RESULTS: There were no diferences in the sex and age of patients and controls. Association with epilepsy was observed for individuals carrying a valine at codon 117 (AlaVal) (OR=13.7, CI: 5.0-37.3, p[lt]0.000000001) and a new polymorphism found at codon 110 (LysAsn) (OR=8.4, CI: 3.0-23.4, p[lt]0.00001), as compared to controls. A mutation in codon 171 (AsnSer), not found in controls, observed in heterozygous was found in 26.5% of the patients (p[lt]0.000000000001) was an independent risk factor for epilepsy. The observed associations did not change when HS and ACD were analyzed separately. None of the patients or controls, present signals or symptoms suggestive of any type of spongiform encephalopathy. Histopathological examinations of ressected tissue from none of the patients exhibited any spongiform degeneration.
CONCLUSIONS: The present data indicates that PrPc gene sequences are risk factors for untreatable epilepsy related to distinct structural and physiopathological subtracts (HS and MCD). PrPc is involved with several physiologic functions, including anti-oxidant properties, neuronal cell adhesion, neurite extension and maintenance and signal transduction. The relevance of the PrPc gene polymorphisms and mutation, herein observed in patients with epilepsy, concerning PrPc function is still unknown. Evaluation of the PrPc gene coding sequence might be used to improve epilepsy diagnosis and treatment.
[Supported by: Work supported by FAPESP (99/07124-8) and FAEPA-HC. RMRPS, PCM and RW are fellows from CAPES, FAPESP and CNPq respectively.]