Background: While common variant non-HLA (human leukocyte antigen) alleles have been associated with MS risk, their role in disease course is less clear. We sought to determine whether established multiple sclerosis (MS) genetic susceptibility factors are associated with relapse rate in children and an independent cohort of adults with MS.

Methods: Genotyping was performed for 182 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 single nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate. Cox regression models were adjusted for sex, genetic ancestry, disease-modifying therapy (DMT), 25-OH vitamin D level and HLA-DRB1*15:01/03 status. Investigation of pediatric subject SNP results was performed using a second cohort of 141 adult MS subjects of Northern European ancestry from the Southern Tasmanian Multiple Sclerosis Longitudinal Study.

Results: For pediatric subjects, 408 relapses were captured over 622 patient-years of follow-up. Four non-HLA risk SNPs (rs11154801, rs650258, rs12212193, rs2303759) were associated with relapses (p < 0.01) in the pediatric subjects. After adjustment for genetic ancestry, sex, age, vitamin D level, DMT use and HLA-DRB1*15 status, having two copies of the MS risk allele within AHI1 (rs11154801) was associated with increased relapses among children (HR = 1.75,95%CI = 1.18-2.48, p = 0.006) and this result was also observed among adults (HR = 1.81,95%CI = 1.05-3.03, p = 0.026).

Conclusions: Our results suggest that the MS genetic risk variant within the gene AHI1 may contribute to disease course in addition to disease susceptibility.

Item Type:	Refereed Article
Keywords:	genetics, multiple sclerosis
Research Division:	Medical and Health Sciences
Research Group:	Neurosciences
Research Field:	Central Nervous System
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Nervous System and Disorders
UTAS Author:	Simpson, S (Dr Steve Simpson JR)
UTAS Author:	Lin, R (Ms Lin)
UTAS Author:	Taylor, BV (Professor Bruce Taylor)
UTAS Author:	Ponsonby, A-L (Professor Anne Ponsonby)
UTAS Author:	Dwyer, T (Professor Terry Dwyer)
UTAS Author:	van der Mei, IAF (Associate Professor Ingrid van der Mei)
ID Code:	127921
Year Published:	2018
Web of Science® Times Cited:	5
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2018-08-22
Last Modified:	2019-03-04
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