Abstract Details

Title Multiple Sclerosis Genetic Susceptibility Factors rs4648356 and rs11154801 Are Associated with Relapse Rate in Pediatric Patients

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 133

Objective

Background BACKGROUND: While genetic susceptibility factors have been identified for adult multiple sclerosis (MS), their effects on disease course in adults or children are unclear. Pediatric MS patients are an ideal population for study, as higher genetic burden may result in earlier MS onset.

Design/Methods DESIGN/METHODS: Genotyping was performed (Illumina 660K platform) for MS or clinically isolated syndrome patients from two Pediatric MS Centers. The top 10 single nucleotide polymorphisms (SNPs) associated with MS risk in adult genome wide association studies were evaluated for association with relapse rate. The SNPs were ranked by p value. Weighted scores of the top 52 SNPs, HLA-DRB1*1501, and SNPs in the KCNJ10 gene were also evaluated. Repeated events models adjusted for disease-modifying therapy, demographic variables, and vitamin D level.

Results RESULTS: For 117 subjects, 266 relapse events were captured over 328 patient-years of follow-up. Two SNPs were associated with relapse hazard rate. For rs4648356 [putative candidate genes membrane metallo-endopeptidase-like 1 (MMEL1) or tetratricopeptide repeat domain 34 (TTC34)], the relapse hazard rate was reduced by 64% for those with 2 copies of the risk allele (HR 0.36, 95%CI: 0.20-0.65, p=0.001). Having 2 copies of risk allele for SNP rs11154801 [Abelson helper integration site 1 (AHI1)] was associated with higher relapse rate (HR 2.08, 95%CI 1.23-3.52, p=0.006) compared to the absence of the risk allele. We did not find an association between weighted genetic risk scores, HLA-DRB1*1501, or KCNJ10 SNPs and relapse hazard rate.

Conclusions CONCLUSIONS: A protective allele associated with the functions of MMEL1 or TTC34 may confer a reduced relapse rate in pediatric MS while the risk allele for AHI1 may be associated with higher relapse rate. Replication of these results is required.

Authors/Disclosures
Jennifer Graves, MD, PhD (UCSD) PRESENTER	Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Graves has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MSJ. The institution of Dr. Graves has received research support from Octave. The institution of Dr. Graves has received research support from Sanofi. The institution of Dr. Graves has received research support from EMD Serono.
	No disclosure on file
Anat Achiron, MD, PhD, FAAN (Sheba Medical Center, Tel-Hashomer)	Dr. Achiron has nothing to disclose.
Anita L. Belman, MD, FAAN	No disclosure on file
Lauren B. Krupp, MD, FAAN (NYU Langone Medical Center)	Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EBIX. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman LaRoche. Dr. krupp has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MMMK. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Patrick, Dolan, and Kaufman. Dr. krupp has received intellectual property interests from a discovery or technology relating to health care.
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center)	The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.

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