Graves, JS and Barcellos, LF and Simpson, S and Belman, A and Lin, R and Taylor, BV and Ponsonby, A-L and Dwyer, T and Krupp, L and Waubant, E and van der Mei, IAF, The multiple sclerosis risk allele within the AHI1 gene is associated with relapses in children and adults, Multiple Sclerosis and Related Disorders, 19 pp. 161-165. ISSN 2211-0348 (2018) [Refereed Article]
Copyright 2017 Elsevier B.V.
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:||Biomedical and Clinical Sciences|
|Research Field:||Central nervous system|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|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 (Professor Ingrid van der Mei)|
|Web of Science® Times Cited:||6|
|Deposited By:||Menzies Institute for Medical Research|
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