Contributions
Abstract: P1071
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Introduction: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disorder of the central nervous system and one of the most common causes of neurological disability among young adults. MS onset is probably triggered by interaction between environmental and genetic factors. Several genetic and environmental risk factors have been identified for MS, however the functional mechanisms leading to MS onset are not fully understood. DNA methylation is an epigenetic modification that affects gene regulation, and may link genetic makeup and environmental exposures in complex diseases such as MS.
Objectives: We investigate the role of DNA methylation in immune cells relevant to MS.
Methods: Genome-wide DNA methylation profiles of CD4+and CD8+ T cells from 94 women with relapsing-remitting MS patients and 94 healthy women were obtained using Illumina Infinium Beadchips. Data was processed in R using the Minfi package, and surrogate variable analysis (SVA) was used to estimate latent variables that might confound results. Genomic regions of differential DNA methylation were identified with the Bumphunter package. Gene expression profiling by microarray was performed in whole blood in a separate population of 1,329 women with MS and 97 healthy women.
Results: We identify differential DNA methylation in five regions close to the SLFN12, HLA-DRB1, ZFP57, MOG and NINJ2 genes. The most consistent signal was DNA hypermethylation of the first exon of SLFN12 in both CD4+ and CD8+ T cells from MS patients compared to healthy controls. In agreement with this, SLFN12 was expressed at a lower level in whole blood from MS patients. SLFN12 encodes a protein of the “schlafen” family, which are transcriptionally regulated by interferons and inhibit retroviral synthesis. Viral exposures are a suggested environmental risk factor for MS, and interferon beta type I has been used to treat MS. This study provides evidence that dysregulation of gene expression through altered DNA methylation may contribute to MS risk.
Disclosure: Dipen P. Sangurdekar and Paola G. Bronson are employees at Biogen, Inc. Stine Marit Moen reports an unrestricted travel grant from Novartis and speaker fees from Biogen Idec and Novartis. Hanne F. Harbo reports personal fees from Biogen Norway, Merck Norway, and Genzyme Norway, and grants and personal fees from Novartis Norway. Pål Berg-Hanse reports grants and personal fees from Novartis and personal fees from Biogen Idec and Teva. Jeannette Lechner-Scott reports grants and personal fees from Biogen, Novartis, and TEVA, and personal fees from Sanofi Genzyme, Roche, and Merck.
Abstract: P1071
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Introduction: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disorder of the central nervous system and one of the most common causes of neurological disability among young adults. MS onset is probably triggered by interaction between environmental and genetic factors. Several genetic and environmental risk factors have been identified for MS, however the functional mechanisms leading to MS onset are not fully understood. DNA methylation is an epigenetic modification that affects gene regulation, and may link genetic makeup and environmental exposures in complex diseases such as MS.
Objectives: We investigate the role of DNA methylation in immune cells relevant to MS.
Methods: Genome-wide DNA methylation profiles of CD4+and CD8+ T cells from 94 women with relapsing-remitting MS patients and 94 healthy women were obtained using Illumina Infinium Beadchips. Data was processed in R using the Minfi package, and surrogate variable analysis (SVA) was used to estimate latent variables that might confound results. Genomic regions of differential DNA methylation were identified with the Bumphunter package. Gene expression profiling by microarray was performed in whole blood in a separate population of 1,329 women with MS and 97 healthy women.
Results: We identify differential DNA methylation in five regions close to the SLFN12, HLA-DRB1, ZFP57, MOG and NINJ2 genes. The most consistent signal was DNA hypermethylation of the first exon of SLFN12 in both CD4+ and CD8+ T cells from MS patients compared to healthy controls. In agreement with this, SLFN12 was expressed at a lower level in whole blood from MS patients. SLFN12 encodes a protein of the “schlafen” family, which are transcriptionally regulated by interferons and inhibit retroviral synthesis. Viral exposures are a suggested environmental risk factor for MS, and interferon beta type I has been used to treat MS. This study provides evidence that dysregulation of gene expression through altered DNA methylation may contribute to MS risk.
Disclosure: Dipen P. Sangurdekar and Paola G. Bronson are employees at Biogen, Inc. Stine Marit Moen reports an unrestricted travel grant from Novartis and speaker fees from Biogen Idec and Novartis. Hanne F. Harbo reports personal fees from Biogen Norway, Merck Norway, and Genzyme Norway, and grants and personal fees from Novartis Norway. Pål Berg-Hanse reports grants and personal fees from Novartis and personal fees from Biogen Idec and Teva. Jeannette Lechner-Scott reports grants and personal fees from Biogen, Novartis, and TEVA, and personal fees from Sanofi Genzyme, Roche, and Merck.