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The multiple sclerosis risk allele within the AHI1 gene is associated with relapses in children and adults

Graves, JS, Barcellos, LF, Simpson Jr, S ORCID: 0000-0001-6521-3056, Belman, A, Lin, R, Taylor, BV, Ponsonby, AL, Dwyer, T, Krupp, L, Waubant, E and van der Mei, IAF ORCID: 0000-0001-9009-7472 2018 , 'The multiple sclerosis risk allele within the AHI1 gene is associated with relapses in children and adults' , Multiple Sclerosis and Related Disorders, vol. 19 , pp. 161-165 , doi: 10.1016/j.msard.2017.10.008.

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Abstract

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 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: Article
Authors/Creators:Graves, JS and Barcellos, LF and Simpson Jr, S and Belman, A and Lin, R and Taylor, BV and Ponsonby, AL and Dwyer, T and Krupp, L and Waubant, E and van der Mei, IAF
Keywords: genetics, multiple sclerosis
Journal or Publication Title: Multiple Sclerosis and Related Disorders
Publisher: Elsevier BV
ISSN: 2211-0348
DOI / ID Number: 10.1016/j.msard.2017.10.008
Copyright Information:

Copyright 2017 Elsevier B.V.

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