Contributions
Abstract: P1129
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background and aims: Multiple Sclerosis (MS) is considered an autoimmune disease, but the exact cause is unknown. Moreover no prognostic factors have been identified.Brain-Derived Neurotrophic Factor (BDNF) serum levels, its Val66Met polymorphism and its methylation levels have been linked to neurological diseases. We verified the presence of possible correlations between the methylation status of the CpG site adjacent to the BDNF-Val66Met polymorphism and the severity of the disease.
Materials and methods: Blood samples was collected from 209 MS patients; genetic analyses were performed to identify the Val66Met polymorphism and its methylation levels.At the time of observation, 126 (60%) of the subjects were affected by relapsing-remitting MS whereas secondary progressive MS was present in 83 (40%) individuals. The course of the disease was assessed by means of a survival analysis in which the outcome event was defined as reaching an EDSS score of 6.Results were analyzed via a regression analysis using the following variables: age;gender;clinical relapses; MRI relapses;annualized relapse rate;annualized MRI relapse rate; treatment; BDNF polymorphism and gene methylation
Results: The Val/Val genotype was carried by 122 subjects (58%); 81 (39%) carried the Val/Met genotype and 6 (3%) the Met/Met genotype.Since the group of patients homozygous for the Met allele was very small, we conducted further analysis considering subjects carrying (Met+) or not carrying (Met-) the Met allele. The mean percentage of methylation was 80.9±17; median=81.The percentage of methylation of subjects carrying the Val/Val (mean=74.6±10.8), Val/Met (mean=94.5±10.7) and Met/Met (mean=28.5±2.7) genotypes was significantly different (F2,206=160.2; p< 0.001).Stratification according to the percentage of the BDNF methylation showed that patients falling below the median (median methylation=81%) were at a higher risk of reaching an EDSS score of 6.
Conclusions: Lower levels of BDNF gene methylation are correlated with a higher rate of progression toward a severe disease. Patients with a more aggressive disease could need higher levels of serum BDNF to sustain the plastic adaptations needed to deal with more extensive SNC damages. This could be achieved by a hypomethylation of the gene that would lead to a higher transcription and translation rate of this neurotrophic factor. These patients, having a more severe prognosis, are also likely to need a quicker and more aggressive therapy.
Disclosure: Nociti V: has received honoraria for scientific advisory boards for Novartis, Teva, Biogen Idec, Sanofi-Aventis Genzyme, and Bayer Schering, has received funding for travel and speaker honoraria from Teva, Biogen Idec, Bayer Schering, Merck Serono, Almirall, Genzyme and Novartis, and receives research support from Almirall.
Santoro M: nothing to disclose
Quaranta D: nothing to disclose
Losavio FA: nothing to disclose
De Fino C: nothing to disclose
Giordano R: nothing to disclose
Palomba N: nothing to disclose
Rossini PM: nothing to disclose
Guerini FR: nothing to disclose
Clerici M: nothing to disclose
Caputo D: nothing to disclose
Mirabella M: has received honoraria for scientific lectures and advisory board activities from Biogen Novartis, Teva, Sanofi Genzyme, Bayer Shering, Merck Serono, Almirall and research support from Merck Serono, Novartis, Teva, Genzyme
Abstract: P1129
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background and aims: Multiple Sclerosis (MS) is considered an autoimmune disease, but the exact cause is unknown. Moreover no prognostic factors have been identified.Brain-Derived Neurotrophic Factor (BDNF) serum levels, its Val66Met polymorphism and its methylation levels have been linked to neurological diseases. We verified the presence of possible correlations between the methylation status of the CpG site adjacent to the BDNF-Val66Met polymorphism and the severity of the disease.
Materials and methods: Blood samples was collected from 209 MS patients; genetic analyses were performed to identify the Val66Met polymorphism and its methylation levels.At the time of observation, 126 (60%) of the subjects were affected by relapsing-remitting MS whereas secondary progressive MS was present in 83 (40%) individuals. The course of the disease was assessed by means of a survival analysis in which the outcome event was defined as reaching an EDSS score of 6.Results were analyzed via a regression analysis using the following variables: age;gender;clinical relapses; MRI relapses;annualized relapse rate;annualized MRI relapse rate; treatment; BDNF polymorphism and gene methylation
Results: The Val/Val genotype was carried by 122 subjects (58%); 81 (39%) carried the Val/Met genotype and 6 (3%) the Met/Met genotype.Since the group of patients homozygous for the Met allele was very small, we conducted further analysis considering subjects carrying (Met+) or not carrying (Met-) the Met allele. The mean percentage of methylation was 80.9±17; median=81.The percentage of methylation of subjects carrying the Val/Val (mean=74.6±10.8), Val/Met (mean=94.5±10.7) and Met/Met (mean=28.5±2.7) genotypes was significantly different (F2,206=160.2; p< 0.001).Stratification according to the percentage of the BDNF methylation showed that patients falling below the median (median methylation=81%) were at a higher risk of reaching an EDSS score of 6.
Conclusions: Lower levels of BDNF gene methylation are correlated with a higher rate of progression toward a severe disease. Patients with a more aggressive disease could need higher levels of serum BDNF to sustain the plastic adaptations needed to deal with more extensive SNC damages. This could be achieved by a hypomethylation of the gene that would lead to a higher transcription and translation rate of this neurotrophic factor. These patients, having a more severe prognosis, are also likely to need a quicker and more aggressive therapy.
Disclosure: Nociti V: has received honoraria for scientific advisory boards for Novartis, Teva, Biogen Idec, Sanofi-Aventis Genzyme, and Bayer Schering, has received funding for travel and speaker honoraria from Teva, Biogen Idec, Bayer Schering, Merck Serono, Almirall, Genzyme and Novartis, and receives research support from Almirall.
Santoro M: nothing to disclose
Quaranta D: nothing to disclose
Losavio FA: nothing to disclose
De Fino C: nothing to disclose
Giordano R: nothing to disclose
Palomba N: nothing to disclose
Rossini PM: nothing to disclose
Guerini FR: nothing to disclose
Clerici M: nothing to disclose
Caputo D: nothing to disclose
Mirabella M: has received honoraria for scientific lectures and advisory board activities from Biogen Novartis, Teva, Sanofi Genzyme, Bayer Shering, Merck Serono, Almirall and research support from Merck Serono, Novartis, Teva, Genzyme