Contributions
Abstract: P415
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Recently, a single nucleotide polymorphism (SNP) rs9828519 in the SLC9A9 gene, a NA+-H+- exchanger, was found to be associated with less treatment response to interferon-beta (IFN-β) in MS patients. In that study more disease activity was reported for carriers of the rs9828519G allele.
Objective: Our aim was to investigate the association of a SLC9A9 gene variant, rs2800, which is in complete linkage disequilibrium with rs9828519, with disease activity in two cohorts of patients treated with IFN-β.
Methods: The two cohorts of IFN-β treated patients had relapsing-remitting MS (RRMS) and began treatment with IFN-β in the years 1995-2008 and 1996-2012, respectively. Samples from the first cohort were obtained for a previously published study, and samples from the second cohort were collected subsequently. Clinical data were obtained from the Danish MS Treatment Registry. Only patients without neutralizing antibodies to IFN-β were included. SNP rs2800 was genotyped in the first cohort using TaqMan allelic discrimination (Life Technologies) and in the second cohort on the MS replication chip designed and conducted by the International MS Genetics Consortium. In the first cohort the relationship between the SLC9A9 rs2800G/A SNP and time to first relapse and time to EDSS progression was analysed by a Kaplan-Meier and Mantel-Cox analysis in 563 IFN-β treated patients. In the second cohort the relationship between the SLC9A9 rs2800G/A SNP and relapse number the two years before treatment (n=756) and during IFN-β therapy (n=682) was analysed by Poisson regression and negative binomial models. Age and sex were included as covariates in the primary analyses.
Results: The minor allele frequency of rs2800G was 0.27 and 0.30 in the two cohorts, respectively. In the first cohort there was no relationship between the genotype of the SLC9A9 SNP and the time to first relapse or time to sustained EDSS progression during two to five years of treatment with IFN-β, respectively. In the second cohort no significant association was observed between number of relapses 2 years prior treatment and the rs2800 SNP genotypes (incidence rate ratio (IRR)GG= 0.97; 95% CI: 0.81-1.17; p=0.79). Likewise, relapses during treatment with IFN-β were not associated with the rs2800 SNP (IRRGG= 1.28; 95% CI: 0.92-1.79; p=0.14).
Conclusion: The SNP rs2800 in the SLC9A9 gene is not associated with relapse risk or disease progression in Danish MS patients treated with interferon-beta.
Disclosure:
Helle Bach Søndergaard has received support for congress participation from Biogen Idec, Genzyme and Teva.
Annette Bang Oturai has served on scientific advisory boards for Novartis, and served as consultant for Biogen Idec; has received support for congress participation from Biogen Idec, Novartis, Sanofi Aventis and Teva; has received speaker honoraria from, Biogen Idec, Novartis, and Sanofi-Aventis.
Nils Koch-Henriksen has received honoraria for lecturing and participation in advisory councils, travel expenses for attending congresses and meetings, and financial support for monitoring the Danish MS Treatment Register from Bayer-Schering, Merck-Serono, BiogenIdec, TEVA, Sanofi-Avensis, and Novartis for the Danish MS Treatment Register.
P. S. Sørensen has received personal compensation for serving on scientific advisory boards, steering committees or independent data monitoring boards for Biogen Idec, Merck Serono, Novartis, Genzyme, Teva Pharmaceutical Industries Ltd., GlaxoSmithKline, medDay Pharmaceuticals and Forward Pharma and has received speaker honoraria from Biogen Idec, Merck Serono, Teva Pharmaceutical Industries Ltd., Genzyme, and Novartis.
Finn Sellebjerg has served on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva, has been on the steering committee of a clinical trial sponsored by Merck Serono, and served as consultant for Biogen Idec and Novo Nordisk; has received support for congress participation from Biogen Idec, Novartis, Sanofi Aventis and Teva; has received speaker honoraria from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Schering-Plough.
Abstract: P415
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Recently, a single nucleotide polymorphism (SNP) rs9828519 in the SLC9A9 gene, a NA+-H+- exchanger, was found to be associated with less treatment response to interferon-beta (IFN-β) in MS patients. In that study more disease activity was reported for carriers of the rs9828519G allele.
Objective: Our aim was to investigate the association of a SLC9A9 gene variant, rs2800, which is in complete linkage disequilibrium with rs9828519, with disease activity in two cohorts of patients treated with IFN-β.
Methods: The two cohorts of IFN-β treated patients had relapsing-remitting MS (RRMS) and began treatment with IFN-β in the years 1995-2008 and 1996-2012, respectively. Samples from the first cohort were obtained for a previously published study, and samples from the second cohort were collected subsequently. Clinical data were obtained from the Danish MS Treatment Registry. Only patients without neutralizing antibodies to IFN-β were included. SNP rs2800 was genotyped in the first cohort using TaqMan allelic discrimination (Life Technologies) and in the second cohort on the MS replication chip designed and conducted by the International MS Genetics Consortium. In the first cohort the relationship between the SLC9A9 rs2800G/A SNP and time to first relapse and time to EDSS progression was analysed by a Kaplan-Meier and Mantel-Cox analysis in 563 IFN-β treated patients. In the second cohort the relationship between the SLC9A9 rs2800G/A SNP and relapse number the two years before treatment (n=756) and during IFN-β therapy (n=682) was analysed by Poisson regression and negative binomial models. Age and sex were included as covariates in the primary analyses.
Results: The minor allele frequency of rs2800G was 0.27 and 0.30 in the two cohorts, respectively. In the first cohort there was no relationship between the genotype of the SLC9A9 SNP and the time to first relapse or time to sustained EDSS progression during two to five years of treatment with IFN-β, respectively. In the second cohort no significant association was observed between number of relapses 2 years prior treatment and the rs2800 SNP genotypes (incidence rate ratio (IRR)GG= 0.97; 95% CI: 0.81-1.17; p=0.79). Likewise, relapses during treatment with IFN-β were not associated with the rs2800 SNP (IRRGG= 1.28; 95% CI: 0.92-1.79; p=0.14).
Conclusion: The SNP rs2800 in the SLC9A9 gene is not associated with relapse risk or disease progression in Danish MS patients treated with interferon-beta.
Disclosure:
Helle Bach Søndergaard has received support for congress participation from Biogen Idec, Genzyme and Teva.
Annette Bang Oturai has served on scientific advisory boards for Novartis, and served as consultant for Biogen Idec; has received support for congress participation from Biogen Idec, Novartis, Sanofi Aventis and Teva; has received speaker honoraria from, Biogen Idec, Novartis, and Sanofi-Aventis.
Nils Koch-Henriksen has received honoraria for lecturing and participation in advisory councils, travel expenses for attending congresses and meetings, and financial support for monitoring the Danish MS Treatment Register from Bayer-Schering, Merck-Serono, BiogenIdec, TEVA, Sanofi-Avensis, and Novartis for the Danish MS Treatment Register.
P. S. Sørensen has received personal compensation for serving on scientific advisory boards, steering committees or independent data monitoring boards for Biogen Idec, Merck Serono, Novartis, Genzyme, Teva Pharmaceutical Industries Ltd., GlaxoSmithKline, medDay Pharmaceuticals and Forward Pharma and has received speaker honoraria from Biogen Idec, Merck Serono, Teva Pharmaceutical Industries Ltd., Genzyme, and Novartis.
Finn Sellebjerg has served on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva, has been on the steering committee of a clinical trial sponsored by Merck Serono, and served as consultant for Biogen Idec and Novo Nordisk; has received support for congress participation from Biogen Idec, Novartis, Sanofi Aventis and Teva; has received speaker honoraria from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Schering-Plough.