Contributions
Abstract: P956
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Objective: We sought to determine whether established multiple sclerosis (MS) genetic susceptibility factors are associated with relapse rate in children and a replication cohort of adults with MS.
Methods: Genotyping was performed for 185 children with MS or clinically isolated syndrome with high risk for MS from two Pediatric MS Centers. They were prospectively followed for relapses. Fifty-two non-HLA MS susceptibility SNPs were both evaluated for association with relapse rate. Cox regression models adjusted for disease-modifying therapy (DMT) use, genetic markers of ancestry and sex. Replication of pediatric subject SNP results was performed using a second cohort of 141 adult MS subjects from the Southern Tasmanian Multiple Sclerosis Longitudinal Study.
Results: Over 622 patient-years of follow-up, 408 relapses were captured. Several non-HLA risk SNPs were associated with relapse hazard (p< 0.05) in the pediatric subjects. After adjustment for HLA-DRB1*15:01, sex, vitamin D level, and DMT, having two copies of risk allele for AHI1 was associated with increased relapses in the pediatric subjects (HR 1.67, 95%CI 1.12-2.49, p=0.012) and this result replicated in the adult subjects (HR 1.81, 95% CI 1.07-3.08, p=0.028). The risk allele downstream of IL22RA2 increased the hazard to relapse associated with low vitamin D in both children (HR 1.59, 95% CI 1.25,2.03, p< 0.001) and adults (HR 1.92, 95% CI 1.20,3.07, p=0.006).
Conclusions: Our results suggest genetic risk variants may also contribute to disease course. We further find genetic modification of vitamin D effects on relapse rate.
Disclosure: Dr. Graves has no relevant disclosures and is supported by grants from the Race to Erase MS, NMSS, Biogen and Genentech.
Dr. Barcellos: No disclosures
Dr. Simpson: No disclosures
Dr. Noble: No disclosures
Dr. Belman: No disclosures
Dr. Lin : No disclosures
Dr. Taylor: No disclosures
Dr. Ponsonby: No disclosures
Dr. Dwyer: No disclosures
Dr. Krupp: No disclosures
Dr. Waubant: No relevant disclosures. She is supported by grants from the NIH, the National MS Society, The Race to Erase MS Foundation. She volunteers on an advisory board for a Novartis trial. She is the site PI for trials with Roche, Biogen and Novartis.
Dr. Van der Mei: No disclosures
Abstract: P956
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Objective: We sought to determine whether established multiple sclerosis (MS) genetic susceptibility factors are associated with relapse rate in children and a replication cohort of adults with MS.
Methods: Genotyping was performed for 185 children with MS or clinically isolated syndrome with high risk for MS from two Pediatric MS Centers. They were prospectively followed for relapses. Fifty-two non-HLA MS susceptibility SNPs were both evaluated for association with relapse rate. Cox regression models adjusted for disease-modifying therapy (DMT) use, genetic markers of ancestry and sex. Replication of pediatric subject SNP results was performed using a second cohort of 141 adult MS subjects from the Southern Tasmanian Multiple Sclerosis Longitudinal Study.
Results: Over 622 patient-years of follow-up, 408 relapses were captured. Several non-HLA risk SNPs were associated with relapse hazard (p< 0.05) in the pediatric subjects. After adjustment for HLA-DRB1*15:01, sex, vitamin D level, and DMT, having two copies of risk allele for AHI1 was associated with increased relapses in the pediatric subjects (HR 1.67, 95%CI 1.12-2.49, p=0.012) and this result replicated in the adult subjects (HR 1.81, 95% CI 1.07-3.08, p=0.028). The risk allele downstream of IL22RA2 increased the hazard to relapse associated with low vitamin D in both children (HR 1.59, 95% CI 1.25,2.03, p< 0.001) and adults (HR 1.92, 95% CI 1.20,3.07, p=0.006).
Conclusions: Our results suggest genetic risk variants may also contribute to disease course. We further find genetic modification of vitamin D effects on relapse rate.
Disclosure: Dr. Graves has no relevant disclosures and is supported by grants from the Race to Erase MS, NMSS, Biogen and Genentech.
Dr. Barcellos: No disclosures
Dr. Simpson: No disclosures
Dr. Noble: No disclosures
Dr. Belman: No disclosures
Dr. Lin : No disclosures
Dr. Taylor: No disclosures
Dr. Ponsonby: No disclosures
Dr. Dwyer: No disclosures
Dr. Krupp: No disclosures
Dr. Waubant: No relevant disclosures. She is supported by grants from the NIH, the National MS Society, The Race to Erase MS Foundation. She volunteers on an advisory board for a Novartis trial. She is the site PI for trials with Roche, Biogen and Novartis.
Dr. Van der Mei: No disclosures