Transcriptionally deficient alleles of prodynorphin gene and the risk to develop temporal lobe epilepsy

KAUFFMAN M, CONSALVO D, GONZALEZ MORON D, KOCHEN S

Boston

Congreso; American Academy of Neurology; 2007

OBJECTIVE: To investigate the role of transcriptionally defficient polymorphic alleles of Prodynorphin (PDYN) gene in the development of Temporal Lobe Epilepsy (TLE). BACKGROUND: Genetic factors could be important for the development of TLE. PDYN might be involved in regulatory mechanism of neuronal synchrony in the hippocampus. The PDYN gene promoter exhibits a functional repetitive motive polymorphism. High repetition alleles (H) are transcriptionally more efficient than low repetition alleles (L). DESIGN/METHODS: We performed an association study in a population of patients with Mesial TLE with Hippocampal Sclerosis (MTEHS) and a systematic revision of the literature. 102 MTEHS patients and 86 healthy controls were included. We investigated the antecedent of family history for epileptic events. The PDYN promoter polymorphism was genotypified by means of a PCR assay. We compared allelic and genotypic frequencies using X2 test. We estimated Odds Ratio (OR) by logistic regression. For meta-analysis, we identified case-control association studies between TLE and PDYN searching in PUBMED. We extracted allelic and genotypic frequencies. We estimated pooled OR using a fixed effects model under dominant and co-dominant heredity. RESULTS: In our population, neither the genotypic and allelic frequencies were different between cases and controls (p=0.61) of the whole cohort nor in the analysis limited to TLE with familial predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p=0,003; OR=1,40; IC 95=1,12-1,74) with a modestly higher risk to develop TLE in the group of patients with familial predisposition. CONCLUSIONS/RELEVANCE: Functional allelic variants in the PDYN promoter could modify the risk to develop TLE in subjects familiarly predisposed. Supported by: Dr. Kauffman has a PhD. Scholarship from CONICET, Ministry of Health, Argentina. Category - Epilepsy SubCategory - Genetics Thursday, MayTo investigate the role of transcriptionally defficient polymorphic alleles of Prodynorphin (PDYN) gene in the development of Temporal Lobe Epilepsy (TLE). BACKGROUND: Genetic factors could be important for the development of TLE. PDYN might be involved in regulatory mechanism of neuronal synchrony in the hippocampus. The PDYN gene promoter exhibits a functional repetitive motive polymorphism. High repetition alleles (H) are transcriptionally more efficient than low repetition alleles (L). DESIGN/METHODS: We performed an association study in a population of patients with Mesial TLE with Hippocampal Sclerosis (MTEHS) and a systematic revision of the literature. 102 MTEHS patients and 86 healthy controls were included. We investigated the antecedent of family history for epileptic events. The PDYN promoter polymorphism was genotypified by means of a PCR assay. We compared allelic and genotypic frequencies using X2 test. We estimated Odds Ratio (OR) by logistic regression. For meta-analysis, we identified case-control association studies between TLE and PDYN searching in PUBMED. We extracted allelic and genotypic frequencies. We estimated pooled OR using a fixed effects model under dominant and co-dominant heredity. RESULTS: In our population, neither the genotypic and allelic frequencies were different between cases and controls (p=0.61) of the whole cohort nor in the analysis limited to TLE with familial predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p=0,003; OR=1,40; IC 95=1,12-1,74) with a modestly higher risk to develop TLE in the group of patients with familial predisposition. CONCLUSIONS/RELEVANCE: Functional allelic variants in the PDYN promoter could modify the risk to develop TLE in subjects familiarly predisposed. Supported by: Dr. Kauffman has a PhD. Scholarship from CONICET, Ministry of Health, Argentina. Category - Epilepsy SubCategory - Genetics Thursday, MayBACKGROUND: Genetic factors could be important for the development of TLE. PDYN might be involved in regulatory mechanism of neuronal synchrony in the hippocampus. The PDYN gene promoter exhibits a functional repetitive motive polymorphism. High repetition alleles (H) are transcriptionally more efficient than low repetition alleles (L). DESIGN/METHODS: We performed an association study in a population of patients with Mesial TLE with Hippocampal Sclerosis (MTEHS) and a systematic revision of the literature. 102 MTEHS patients and 86 healthy controls were included. We investigated the antecedent of family history for epileptic events. The PDYN promoter polymorphism was genotypified by means of a PCR assay. We compared allelic and genotypic frequencies using X2 test. We estimated Odds Ratio (OR) by logistic regression. For meta-analysis, we identified case-control association studies between TLE and PDYN searching in PUBMED. We extracted allelic and genotypic frequencies. We estimated pooled OR using a fixed effects model under dominant and co-dominant heredity. RESULTS: In our population, neither the genotypic and allelic frequencies were different between cases and controls (p=0.61) of the whole cohort nor in the analysis limited to TLE with familial predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p=0,003; OR=1,40; IC 95=1,12-1,74) with a modestly higher risk to develop TLE in the group of patients with familial predisposition. CONCLUSIONS/RELEVANCE: Functional allelic variants in the PDYN promoter could modify the risk to develop TLE in subjects familiarly predisposed. Supported by: Dr. Kauffman has a PhD. Scholarship from CONICET, Ministry of Health, Argentina. Category - Epilepsy SubCategory - Genetics Thursday, MayDESIGN/METHODS: We performed an association study in a population of patients with Mesial TLE with Hippocampal Sclerosis (MTEHS) and a systematic revision of the literature. 102 MTEHS patients and 86 healthy controls were included. We investigated the antecedent of family history for epileptic events. The PDYN promoter polymorphism was genotypified by means of a PCR assay. We compared allelic and genotypic frequencies using X2 test. We estimated Odds Ratio (OR) by logistic regression. For meta-analysis, we identified case-control association studies between TLE and PDYN searching in PUBMED. We extracted allelic and genotypic frequencies. We estimated pooled OR using a fixed effects model under dominant and co-dominant heredity. RESULTS: In our population, neither the genotypic and allelic frequencies were different between cases and controls (p=0.61) of the whole cohort nor in the analysis limited to TLE with familial predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p=0,003; OR=1,40; IC 95=1,12-1,74) with a modestly higher risk to develop TLE in the group of patients with familial predisposition. CONCLUSIONS/RELEVANCE: Functional allelic variants in the PDYN promoter could modify the risk to develop TLE in subjects familiarly predisposed. Supported by: Dr. Kauffman has a PhD. Scholarship from CONICET, Ministry of Health, Argentina. Category - Epilepsy SubCategory - Genetics Thursday, May2 test. We estimated Odds Ratio (OR) by logistic regression. For meta-analysis, we identified case-control association studies between TLE and PDYN searching in PUBMED. We extracted allelic and genotypic frequencies. We estimated pooled OR using a fixed effects model under dominant and co-dominant heredity. RESULTS: In our population, neither the genotypic and allelic frequencies were different between cases and controls (p=0.61) of the whole cohort nor in the analysis limited to TLE with familial predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p=0,003; OR=1,40; IC 95=1,12-1,74) with a modestly higher risk to develop TLE in the group of patients with familial predisposition. CONCLUSIONS/RELEVANCE: Functional allelic variants in the PDYN promoter could modify the risk to develop TLE in subjects familiarly predisposed. Supported by: Dr. Kauffman has a PhD. Scholarship from CONICET, Ministry of Health, Argentina. Category - Epilepsy SubCategory - Genetics Thursday, MayRESULTS: In our population, neither the genotypic and allelic frequencies were different between cases and controls (p=0.61) of the whole cohort nor in the analysis limited to TLE with familial predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117 healthy controls. We found an association between L allele (p=0,003; OR=1,40; IC 95=1,12-1,74) with a modestly higher risk to develop TLE in the group of patients with familial predisposition. CONCLUSIONS/RELEVANCE: Functional allelic variants in the PDYN promoter could modify the risk to develop TLE in subjects familiarly predisposed. Supported by: Dr. Kauffman has a PhD. Scholarship from CONICET, Ministry of Health, Argentina. Category - Epilepsy SubCategory - Genetics Thursday, MayCONCLUSIONS/RELEVANCE: Functional allelic variants in the PDYN promoter could modify the risk to develop TLE in subjects familiarly predisposed. Supported by: Dr. Kauffman has a PhD. Scholarship from CONICET, Ministry of Health, Argentina. Category - Epilepsy SubCategory - Genetics Thursday, May